{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:36:59Z","timestamp":1793828219131,"version":"4.6.1"},"reference-count":363,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T00:00:00Z","timestamp":1639440000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Neurosci"],"published-print":{"date-parts":[[2022,2]]},"DOI":"10.1038\/s41583-021-00542-9","type":"journal-article","created":{"date-parts":[[2021,12,14]],"date-time":"2021-12-14T06:03:55Z","timestamp":1639461835000},"page":"115-128","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":231,"title":["Motor and non-motor circuit disturbances in early Parkinson disease: which happens first?"],"prefix":"10.1038","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4257-1325","authenticated-orcid":false,"given":"Javier","family":"Blesa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guglielmo","family":"Foffani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-9045","authenticated-orcid":false,"given":"Benjamin","family":"Dehay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0410-4638","authenticated-orcid":false,"given":"Erwan","family":"Bezard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6996-8613","authenticated-orcid":false,"given":"Jose A.","family":"Obeso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,12,14]]},"reference":[{"key":"542_CR1","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/S1474-4422(06)70471-9","volume":"5","author":"LM de Lau","year":"2006","unstructured":"de Lau, L. M. & Breteler, M. M. Epidemiology of Parkinson\u2019s disease. Lancet Neurol. 5, 525\u2013535 (2006).","journal-title":"Lancet Neurol."},{"key":"542_CR2","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1007\/s00702-017-1686-y","volume":"124","author":"O-B Tysnes","year":"2017","unstructured":"Tysnes, O.-B. & Storstein, A. Epidemiology of Parkinson\u2019s disease. J. Neural Transm. 124, 901\u2013905 (2017).","journal-title":"J. Neural Transm."},{"key":"542_CR3","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1002\/mds.23878","volume":"26","author":"J-P Bach","year":"2011","unstructured":"Bach, J.-P., Ziegler, U., Deuschl, G., Dodel, R. & Doblhammer-Reiter, G. Projected numbers of people with movement disorders in the years 2030 and 2050. Mov. Disord. 26, 2286\u20132290 (2011).","journal-title":"Mov. Disord."},{"key":"542_CR4","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1212\/01.wnl.0000247740.47667.03","volume":"68","author":"ER Dorsey","year":"2007","unstructured":"Dorsey, E. R. et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology 68, 384\u2013386 (2007).","journal-title":"Neurology"},{"key":"542_CR5","doi-asserted-by":"publisher","first-page":"2284","DOI":"10.1016\/S0140-6736(21)00218-X","volume":"397","author":"BR Bloem","year":"2021","unstructured":"Bloem, B. R., Okun, M. S. & Klein, C. Parkinson\u2019s disease. Lancet 397, 2284\u20132303 (2021).","journal-title":"Lancet"},{"key":"542_CR6","doi-asserted-by":"publisher","first-page":"1643","DOI":"10.1002\/mds.27431","volume":"33","author":"D Berg","year":"2018","unstructured":"Berg, D. et al. Movement disorder society criteria for clinically established early Parkinson\u2019s disease. Mov. Disord. 33, 1643\u20131646 (2018). This study describes high-specificity criteria for de novo PD according to the International Parkinson and Movement Disorder Society.","journal-title":"Mov. Disord."},{"key":"542_CR7","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1038\/nrn.2017.62","volume":"18","author":"AHV Schapira","year":"2017","unstructured":"Schapira, A. H. V., Chaudhuri, K. R. & Jenner, P. Non-motor features of Parkinson disease. Nat. Rev. Neurosci. 18, 435\u2013450 (2017).","journal-title":"Nat. Rev. Neurosci."},{"key":"542_CR8","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1038\/nrneurol.2016.152","volume":"12","author":"RB Postuma","year":"2016","unstructured":"Postuma, R. B. & Berg, D. Advances in markers of prodromal Parkinson disease. Nat. Rev. Neurol. 12, 622\u2013634 (2016).","journal-title":"Nat. Rev. Neurol."},{"key":"542_CR9","doi-asserted-by":"publisher","first-page":"277","DOI":"10.3233\/JPD-2011-11046","volume":"1","author":"L Parkkinen","year":"2011","unstructured":"Parkkinen, L. et al. Disentangling the relationship between Lewy bodies and nigral neuronal loss in Parkinson\u2019s disease. J. Parkinsons. Dis. 1, 277\u2013286 (2011).","journal-title":"J. Parkinsons. Dis."},{"key":"542_CR10","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.neurobiolaging.2008.03.015","volume":"31","author":"S Greffard","year":"2010","unstructured":"Greffard, S. et al. A stable proportion of Lewy body bearing neurons in the substantia nigra suggests a model in which the Lewy body causes neuronal death. Neurobiol. Aging 31, 99\u2013103 (2010).","journal-title":"Neurobiol. Aging"},{"key":"542_CR11","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1007\/BF01249445","volume":"38","author":"P Riederer","year":"1976","unstructured":"Riederer, P. & Wuketich, S. Time course of nigrostriatal degeneration in Parkinson\u2019s disease \u2014 a detailed study of influential factors in human brain amine analysis. J. Neural Transm. 38, 277\u2013301 (1976).","journal-title":"J. Neural Transm."},{"key":"542_CR12","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","volume":"114","author":"JMM Fearnley","year":"1991","unstructured":"Fearnley, J. M. M. & Lees, A. J. J. Ageing and Parkinson\u2019s disease: substantia nigra regional selectivity. Brain 114, 2283\u20132301 (1991). This seminal paper studied the micro-architecture of the SNpc in control cases of varying age and patients with PD, showing that the ventral tier is the most vulnerable region, and estimated the pre-symptomatic phase of PD to be about 5 years before the diagnosis.","journal-title":"Brain"},{"key":"542_CR13","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","volume":"24","author":"H Braak","year":"2003","unstructured":"Braak, H. et al. Staging of brain pathology related to sporadic Parkinson\u2019s disease. Neurobiol. Aging 24, 197\u2013211 (2003).","journal-title":"Neurobiol. Aging"},{"key":"542_CR14","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1016\/j.tins.2016.09.003","volume":"39","author":"NP Visanji","year":"2016","unstructured":"Visanji, N. P. et al. \u03b1-Synuclein-based animal models of Parkinson\u2019s disease: challenges and opportunities in a new era. Trends Neurosci. 39, 750\u2013762 (2016).","journal-title":"Trends Neurosci."},{"key":"542_CR15","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1016\/j.neuron.2019.05.035","volume":"103","author":"S Kim","year":"2019","unstructured":"Kim, S. et al. Transneuronal propagation of pathologic \u03b1-synuclein from the gut to the brain models Parkinson\u2019s disease. Neuron 103, 627\u2013641.e7 (2019).","journal-title":"Neuron"},{"key":"542_CR16","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1111\/j.1365-2990.2007.00874.x","volume":"33","author":"CH Hawkes","year":"2007","unstructured":"Hawkes, C. H., Del Tredici, K. & Braak, H. Parkinson\u2019s disease: a dual-hit hypothesis. Neuropathol. Appl. Neurobiol. 33, 599\u2013614 (2007).","journal-title":"Neuropathol. Appl. Neurobiol."},{"issue":"s1","key":"542_CR17","doi-asserted-by":"publisher","first-page":"S71","DOI":"10.3233\/JPD-179001","volume":"7","author":"H Braak","year":"2017","unstructured":"Braak, H. & Del Tredici, K. Neuropathological staging of brain pathology in sporadic Parkinson\u2019s disease: separating the wheat from the chaff. J. Parkinsons Dis. 7 (s1), S71\u2013S85 (2017).","journal-title":"J. Parkinsons Dis."},{"key":"542_CR18","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1038\/nrn.2016.178","volume":"18","author":"DJ Surmeier","year":"2017","unstructured":"Surmeier, D. J., Obeso, J. A. & Halliday, G. M. Selective neuronal vulnerability in Parkinson disease. Nat. Rev. Neurosci. 18, 101\u2013113 (2017). This review discusses the evidence for and against the spreading of Lewy pathology model as well as evidence that cell-autonomous factors govern both \u03b1-syn pathology and neuronal death.","journal-title":"Nat. Rev. Neurosci."},{"key":"542_CR19","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1002\/mds.25952","volume":"29","author":"AA Dijkstra","year":"2014","unstructured":"Dijkstra, A. A. et al. Stage-dependent nigral neuronal loss in incidental Lewy body and Parkinson\u2019s disease. Mov. Disord. 29, 1244\u20131251 (2014).","journal-title":"Mov. Disord."},{"key":"542_CR20","doi-asserted-by":"publisher","first-page":"9799","DOI":"10.1523\/JNEUROSCI.1787-16.2017","volume":"37","author":"D James Surmeier","year":"2017","unstructured":"James Surmeier, D., Obeso, J. A. & Halliday, G. M. Parkinson\u2019s disease is not simply a prion disorder. J. Neurosci. 37, 9799\u20139807 (2017).","journal-title":"J. Neurosci."},{"issue":"Suppl. 1","key":"542_CR21","doi-asserted-by":"publisher","first-page":"S76","DOI":"10.1002\/mds.22783","volume":"25","author":"RE Burke","year":"2010","unstructured":"Burke, R. E. Evaluation of the Braak staging scheme for Parkinson\u2019s disease: introduction to a panel presentation. Mov. Disord. 25 (Suppl. 1), S76\u2013S77 (2010).","journal-title":"Mov. Disord."},{"key":"542_CR22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-008-0406-y","volume":"116","author":"KA Jellinger","year":"2008","unstructured":"Jellinger, K. A. A critical reappraisal of current staging of Lewy-related pathology in human brain. Acta Neuropathol. 116, 1\u201316 (2008).","journal-title":"Acta Neuropathol."},{"key":"542_CR23","first-page":"1092","volume":"15","author":"E Bezard","year":"2001","unstructured":"Bezard, E., Crossman, A. R., Gross, C. E. & Brotchie, J. M. Structures outside the basal ganglia may compensate for dopamine loss in the presymptomatic stages of Parkinson\u2019s disease. FASEB J. 15, 1092\u20131094 (2001).","journal-title":"FASEB J."},{"key":"542_CR24","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0166-2236(03)00038-9","volume":"26","author":"E Bezard","year":"2003","unstructured":"Bezard, E., Gross, C. E. & Brotchie, J. M. Presymptomatic compensation in Parkinson\u2019s disease is not dopamine-mediated. Trends Neurosci. 26, 215\u2013221 (2003).","journal-title":"Trends Neurosci."},{"key":"542_CR25","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.expneurol.2017.10.002","volume":"298","author":"J Blesa","year":"2017","unstructured":"Blesa, J. et al. Compensatory mechanisms in Parkinson\u2019s disease: circuits adaptations and role in disease modification. Exp. Neurol. 298, 148\u2013161 (2017). This paper reviews the evidence for the role of the best known and other possible compensatory mechanisms in early stages of PD.","journal-title":"Exp. Neurol."},{"key":"542_CR26","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1002\/mds.28462","volume":"36","author":"MHG Monje","year":"2021","unstructured":"Monje, M. H. G. et al. Motor onset topography and progression in Parkinson\u2019s disease: the upper limb is first. Mov. Disord. 36, 905\u2013915 (2021).","journal-title":"Mov. Disord."},{"issue":"S1","key":"542_CR27","doi-asserted-by":"publisher","first-page":"S19","DOI":"10.3233\/JPD-181457","volume":"8","author":"D Berg","year":"2018","unstructured":"Berg, D. & Postuma, R. B. From prodromal to overt Parkinson\u2019s disease: Towards a new definition in the year 2040. J. Parkinsons Dis. 8 (S1), S19\u2013S23 (2018).","journal-title":"J. Parkinsons Dis."},{"key":"542_CR28","doi-asserted-by":"publisher","first-page":"594","DOI":"10.1002\/mds.28493","volume":"36","author":"C Fearon","year":"2021","unstructured":"Fearon, C., Lang, A. E. & Espay, A. J. The logic and pitfalls of Parkinson\u2019s disease as \u201cbrain-first\u201d versus \u201cbody-first\u201d subtypes. Mov. Disord. 36, 594\u2013598 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR29","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00401-009-0538-8","volume":"117","author":"TG Beach","year":"2009","unstructured":"Beach, T. G. et al. Unified staging system for Lewy body disorders: correlation with nigrostriatal degeneration, cognitive impairment and motor dysfunction. Acta Neuropathol. 117, 613\u2013634 (2009).","journal-title":"Acta Neuropathol."},{"key":"542_CR30","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1093\/jnen\/nlz080","volume":"78","author":"CH Adler","year":"2019","unstructured":"Adler, C. H. et al. Unified staging system for Lewy body disorders: clinicopathologic correlations and comparison to Braak staging. J. Neuropathol. Exp. Neurol. 78, 891\u2013899 (2019).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"542_CR31","doi-asserted-by":"publisher","first-page":"848","DOI":"10.1016\/0016-5085(84)90079-9","volume":"87","author":"SJ Qualman","year":"1984","unstructured":"Qualman, S. J., Haupt, H. M., Yang, P. & Hamilton, S. R. Esophageal Lewy bodies associated with ganglion cell loss in achalasia. Similarity to Parkinson\u2019s disease. Gastroenterology 87, 848\u2013856 (1984).","journal-title":"Gastroenterology"},{"key":"542_CR32","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.neulet.2005.11.012","volume":"396","author":"H Braak","year":"2006","unstructured":"Braak, H., de Vos, R. A. I., Bohl, J. & Del Tredici, K. Gastric alpha-synuclein immunoreactive inclusions in Meissner\u2019s and Auerbach\u2019s plexuses in cases staged for Parkinson\u2019s disease-related brain pathology. Neurosci. Lett. 396, 67\u201372 (2006).","journal-title":"Neurosci. Lett."},{"key":"542_CR33","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/BF00687767","volume":"76","author":"K Wakabayashi","year":"1988","unstructured":"Wakabayashi, K., Takahashi, H., Takeda, S., Ohama, E. & Ikuta, F. Parkinson\u2019s disease: the presence of Lewy bodies in Auerbach\u2019s and Meissner\u2019s plexuses. Acta Neuropathol. 76, 217\u2013221 (1988).","journal-title":"Acta Neuropathol."},{"key":"542_CR34","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1002\/mds.25020","volume":"27","author":"KM Shannon","year":"2012","unstructured":"Shannon, K. M., Keshavarzian, A., Dodiya, H. B., Jakate, S. & Kordower, J. H. Is alpha-synuclein in the colon a biomarker for premotor Parkinson\u2019s disease? Evidence from 3 cases. Mov. Disord. 27, 716\u2013719 (2012).","journal-title":"Mov. Disord."},{"key":"542_CR35","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1007\/s00401-013-1214-6","volume":"127","author":"D Hilton","year":"2014","unstructured":"Hilton, D. et al. Accumulation of alpha-synuclein in the bowel of patients in the pre-clinical phase of Parkinson\u2019s disease. Acta Neuropathol. 127, 235\u2013241 (2014).","journal-title":"Acta Neuropathol."},{"key":"542_CR36","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1002\/ana.24648","volume":"79","author":"MG Stokholm","year":"2016","unstructured":"Stokholm, M. G., Danielsen, E. H., Hamilton-Dutoit, S. J. & Borghammer, P. Pathological alpha-synuclein in gastrointestinal tissues from prodromal Parkinson disease patients. Ann. Neurol. 79, 940\u2013949 (2016).","journal-title":"Ann. Neurol."},{"key":"542_CR37","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.1212\/WNL.0000000000002126","volume":"85","author":"FS Sprenger","year":"2015","unstructured":"Sprenger, F. S. et al. Enteric nervous system alpha-synuclein immunoreactivity in idiopathic REM sleep behavior disorder. Neurology 85, 1761\u20131768 (2015).","journal-title":"Neurology"},{"key":"542_CR38","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1002\/ana.24448","volume":"78","author":"E Svensson","year":"2015","unstructured":"Svensson, E. et al. Vagotomy and subsequent risk of Parkinson\u2019s disease. Ann. Neurol. 78, 522\u2013529 (2015).","journal-title":"Ann. Neurol."},{"key":"542_CR39","doi-asserted-by":"publisher","first-page":"1996","DOI":"10.1212\/WNL.0000000000003961","volume":"88","author":"B Liu","year":"2017","unstructured":"Liu, B. et al. Vagotomy and Parkinson disease: a Swedish register-based matched-cohort study. Neurology 88, 1996\u20132002 (2017).","journal-title":"Neurology"},{"key":"542_CR40","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1212\/WNL.0000000000003969","volume":"88","author":"P Borghammer","year":"2017","unstructured":"Borghammer, P. & Hamani, C. Preventing Parkinson disease by vagotomy: fact or fiction? Neurology 88, 1982\u20131983 (2017).","journal-title":"Neurology"},{"key":"542_CR41","doi-asserted-by":"publisher","first-page":"1011","DOI":"10.1002\/ana.24531","volume":"78","author":"O-B Tysnes","year":"2015","unstructured":"Tysnes, O.-B. et al. Does vagotomy reduce the risk of Parkinson\u2019s disease? Ann. Neurol. 78, 1011\u20131012 (2015).","journal-title":"Ann. Neurol."},{"key":"542_CR42","doi-asserted-by":"publisher","first-page":"1114","DOI":"10.1002\/mds.26605","volume":"31","author":"CH Adler","year":"2016","unstructured":"Adler, C. H. & Beach, T. G. Neuropathological basis of nonmotor manifestations of Parkinson\u2019s disease. Mov. Disord. 31, 1114\u20131119 (2016). This review discusses neuropathological findings that may underlie nonmotor symptoms that either predate motor findings or occur as PD progresses.","journal-title":"Mov. Disord."},{"key":"542_CR43","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/s00401-010-0664-3","volume":"119","author":"TG Beach","year":"2010","unstructured":"Beach, T. G. et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 119, 689\u2013702 (2010).","journal-title":"Acta Neuropathol."},{"key":"542_CR44","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1097\/nen.0b013e3180517454","volume":"66","author":"Y Fumimura","year":"2007","unstructured":"Fumimura, Y. et al. Analysis of the adrenal gland is useful for evaluating pathology of the peripheral autonomic nervous system in Lewy body disease. J. Neuropathol. Exp. Neurol. 66, 354\u2013362 (2007).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"542_CR45","doi-asserted-by":"publisher","first-page":"1833","DOI":"10.3233\/JPD-212733","volume":"11","author":"TG Beach","year":"2021","unstructured":"Beach, T. G. et al. Vagus nerve and stomach synucleinopathy in Parkinson\u2019s disease, incidental Lewy body disease, and normal elderly subjects: evidence against the \u201cBody-First\u201d hypothesis. J. Parkinsons. Dis. 11, 1833\u20131843 (2021). This study in a large cohort of individuals shows absence of phosphorylated \u03b1-syn in the vagus nerve or stomach of individuals without brain phosphorylated synuclein pathology, while those with brain pathology (incidental LB and PD) were positive, supporting initiation of the pathology first in the brain.","journal-title":"J. Parkinsons. Dis."},{"key":"542_CR46","doi-asserted-by":"publisher","first-page":"2085","DOI":"10.1002\/mds.28615","volume":"36","author":"B Huynh","year":"2021","unstructured":"Huynh, B., Fu, Y., Kirik, D., Shine, J. M. & Halliday, G. M. Comparison of locus coeruleus pathology with nigral and forebrain pathology in Parkinson\u2019s disease. Mov. Disord. 36, 2085\u20132093 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR47","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1111\/j.1365-2990.2007.00923.x","volume":"34","author":"ME Kalaitzakis","year":"2008","unstructured":"Kalaitzakis, M. E., Graeber, M. B., Gentleman, S. M. & Pearce, R. K. B. The dorsal motor nucleus of the vagus is not an obligatory trigger site of Parkinson\u2019s disease: a critical analysis of \u03b1-synuclein staging. Neuropathol. Appl. Neurobiol. 34, 284\u2013295 (2008).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"542_CR48","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1586\/ern.12.47","volume":"12","author":"G Halliday","year":"2012","unstructured":"Halliday, G., McCann, H. & Shepherd, C. Evaluation of the Braak hypothesis: how far can it explain the pathogenesis of Parkinson\u2019s disease? Expert Rev. Neurother. 12, 673\u2013686 (2012).","journal-title":"Expert Rev. Neurother."},{"key":"542_CR49","doi-asserted-by":"publisher","first-page":"2307","DOI":"10.1212\/WNL.0b013e318278fe32","volume":"79","author":"JM Milber","year":"2012","unstructured":"Milber, J. M. et al. Lewy pathology is not the first sign of degeneration in vulnerable neurons in Parkinson disease. Neurology 79, 2307\u20132314 (2012).","journal-title":"Neurology"},{"key":"542_CR50","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/mds.26421","volume":"31","author":"H McCann","year":"2016","unstructured":"McCann, H., Cartwright, H. & Halliday, G. M. Neuropathology of \u03b1-synuclein propagation and Braak hypothesis. Mov. Disord. 31, 152\u2013160 (2016).","journal-title":"Mov. Disord."},{"key":"542_CR51","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1002\/mds.22971","volume":"25","author":"CH Adler","year":"2010","unstructured":"Adler, C. H. et al. Incidental Lewy body disease: clinical comparison to a control cohort. Mov. Disord. 25, 642\u2013646 (2010).","journal-title":"Mov. Disord."},{"key":"542_CR52","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1212\/WNL.0000000000002102","volume":"85","author":"D Iacono","year":"2015","unstructured":"Iacono, D. et al. Parkinson disease and incidental Lewy body disease: just a question of time? Neurology 85, 1670\u20131679 (2015).","journal-title":"Neurology"},{"key":"542_CR53","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1001\/archneur.65.8.1074","volume":"65","author":"A DelleDonne","year":"2008","unstructured":"DelleDonne, A. et al. Incidental Lewy body disease and preclinical Parkinson disease. Arch. Neurol. 65, 1074\u20131080 (2008).","journal-title":"Arch. Neurol."},{"key":"542_CR54","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1007\/s00401-008-0345-7","volume":"115","author":"DW Dickson","year":"2008","unstructured":"Dickson, D. W. et al. Evidence that incidental Lewy body disease is pre-symptomatic Parkinson\u2019s disease. Acta Neuropathol. 115, 437\u2013444 (2008).","journal-title":"Acta Neuropathol."},{"key":"542_CR55","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1007\/s00401-007-0313-7","volume":"115","author":"TG Beach","year":"2008","unstructured":"Beach, T. G. et al. Reduced striatal tyrosine hydroxylase in incidental Lewy body disease. Acta Neuropathol. 115, 445\u2013451 (2008).","journal-title":"Acta Neuropathol."},{"key":"542_CR56","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1001\/jamaneurol.2013.172","volume":"70","author":"KM Doherty","year":"2013","unstructured":"Doherty, K. M. et al. Parkin disease: a clinicopathologic entity? JAMA Neurol. 70, 571 (2013).","journal-title":"JAMA Neurol."},{"key":"542_CR57","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1001\/jamaneurol.2014.2704","volume":"72","author":"LV Kalia","year":"2015","unstructured":"Kalia, L. V. et al. Clinical correlations with lewy body pathology in LRRK2-related parkinson disease. JAMA Neurol. 72, 100 (2015).","journal-title":"JAMA Neurol."},{"key":"542_CR58","first-page":"6838965","volume":"2018","author":"KK Johansen","year":"2018","unstructured":"Johansen, K. K., Torp, S. H., Farrer, M. J., Gustavsson, E. K. & Aasly, J. O. A case of Parkinson\u2019s disease with no lewy body pathology due to a homozygous exon deletion in parkin. Case Rep. Neurol. Med. 2018, 6838965 (2018).","journal-title":"Case Rep. Neurol. Med."},{"key":"542_CR59","doi-asserted-by":"publisher","first-page":"2212","DOI":"10.1212\/WNL.0000000000002744","volume":"86","author":"M Takanashi","year":"2016","unstructured":"Takanashi, M., Li, Y. & Hattori, N. Absence of Lewy pathology associated with PINK1 homozygous mutation. Neurology 86, 2212\u20132213 (2016).","journal-title":"Neurology"},{"key":"542_CR60","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1002\/mds.27193","volume":"32","author":"SA Schneider","year":"2017","unstructured":"Schneider, S. A. & Alcalay, R. N. Neuropathology of genetic synucleinopathies with parkinsonism: review of the literature. Mov. Disord. 32, 1504\u20131523 (2017).","journal-title":"Mov. Disord."},{"key":"542_CR61","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1038\/s41583-020-00416-6","volume":"22","author":"MB Fares","year":"2021","unstructured":"Fares, M. B., Jagannath, S. & Lashuel, H. A. Reverse engineering Lewy bodies: how far have we come and how far can we go? Nat. Rev. Neurosci. 22, 111\u2013131 (2021). This review discusses current knowledge of \u03b1-syn pathology, including the biochemical, structural and morphological features of LB, their biochemical composition and ultsrastructural properties, how they evolve and spread, and their role in neurodegeneration.","journal-title":"Nat. Rev. Neurosci."},{"key":"542_CR62","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.cbpa.2021.05.006","volume":"64","author":"HA Lashuel","year":"2021","unstructured":"Lashuel, H. A. Rethinking protein aggregation and drug discovery in neurodegenerative diseases: why we need to embrace complexity? Curr. Opin. Chem. Biol. 64, 67\u201375 (2021). This stimulating article challenges traditional views about the composition, properties and diversity of protein pathologies in the brain, embracing the complexity of proteinopathies to better understand the molecular mechanisms underpinning most neurodegenerative diseases.","journal-title":"Curr. Opin. Chem. Biol."},{"key":"542_CR63","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/s41531-021-00203-9","volume":"7","author":"LMA Oliveira","year":"2021","unstructured":"Oliveira, L. M. A. et al. Alpha-synuclein research: defining strategic moves in the battle against Parkinson\u2019s disease. NPJ Parkinsons Dis. 7, 65 (2021).","journal-title":"NPJ Parkinsons Dis."},{"key":"542_CR64","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1056\/NEJM199601113340202","volume":"334","author":"DA Bennett","year":"1996","unstructured":"Bennett, D. A. et al. Prevalence of Parkinsonian signs and associated mortality in a community population of older people. N. Engl. J. Med. 334, 71\u201376 (1996).","journal-title":"N. Engl. J. Med."},{"key":"542_CR65","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1002\/mds.23499","volume":"26","author":"A Gaenslen","year":"2011","unstructured":"Gaenslen, A., Swid, I., Liepelt-Scarfone, I., Godau, J. & Berg, D. The patients\u2019 perception of prodromal symptoms before the initial diagnosis of Parkinson\u2019s disease. Mov. Disord. 26, 653\u2013658 (2011).","journal-title":"Mov. Disord."},{"key":"542_CR66","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1001\/archneur.63.3.noc50312","volume":"63","author":"LML De Lau","year":"2006","unstructured":"De Lau, L. M. L., Koudstaal, P. J., Hofman, A. & Breteler, M. M. B. Subjective complaints precede Parkinson disease: the Rotterdam study. Arch. Neurol. 63, 362\u2013365 (2006).","journal-title":"Arch. Neurol."},{"key":"542_CR67","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1176\/jnp.14.2.223","volume":"14","author":"J Parkinson","year":"1817","unstructured":"Parkinson, J. An essay on the shaking palsy. J. Neuropsychiatry Clin. Neurosci. 14, 223\u2013236 (1817). It is very interesting that the original description highlighted the motor manifestations, nowadays associated with nigrostriatal denervation, as well as some classic non-motor symptoms.","journal-title":"J. Neuropsychiatry Clin. Neurosci."},{"key":"542_CR68","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/0022-510X(72)90002-0","volume":"15","author":"JE McLennan","year":"1972","unstructured":"McLennan, J. E., Nakano, K., Tyler, H. R. & Schwab, R. S. Micrographia in Parkinson\u2019s disease. J. Neurol. Sci. 15, 141\u2013152 (1972).","journal-title":"J. Neurol. Sci."},{"key":"542_CR69","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1136\/jnnp.55.3.181","volume":"55","author":"AJ Hughes","year":"1992","unstructured":"Hughes, A. J., Daniel, S. E., Kilford, L. & Lees, A. J. Accuracy of clinical diagnosis of idiopathic Parkinson\u2019s disease: a clinico-pathological study of 100 cases. J. Neurol. Neurosurg. Psychiatry 55, 181\u2013184 (1992).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR70","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1093\/brain\/aww291","volume":"140","author":"SKL Darweesh","year":"2017","unstructured":"Darweesh, S. K. L. et al. Trajectories of prediagnostic functioning in Parkinson\u2019s disease. Brain 140, 429\u2013441 (2017).","journal-title":"Brain"},{"key":"542_CR71","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1001\/jamaneurol.2017.0985","volume":"74","author":"D Jennings","year":"2017","unstructured":"Jennings, D. et al. Conversion to Parkinson disease in the PARS hyposmic and dopamine transporter-deficit prodromal cohort. JAMA Neurol. 74, 933\u2013940 (2017).","journal-title":"JAMA Neurol."},{"key":"542_CR72","doi-asserted-by":"publisher","first-page":"2970","DOI":"10.1093\/brain\/awp209","volume":"132","author":"R Nandhagopal","year":"2009","unstructured":"Nandhagopal, R. et al. Longitudinal progression of sporadic Parkinson\u2019s disease: a multi-tracer positron emission tomography study. Brain 132, 2970\u20132979 (2009).","journal-title":"Brain"},{"issue":"Suppl. 2","key":"542_CR73","doi-asserted-by":"publisher","first-page":"S2","DOI":"10.1212\/WNL.51.2_Suppl_2.S2","volume":"51","author":"O Hornykiewicz","year":"1998","unstructured":"Hornykiewicz, O. Biochemical aspects of Parkinson\u2019s disease. Neurology 51 (Suppl. 2), S2\u2013S9 (1998).","journal-title":"Neurology"},{"key":"542_CR74","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/JPD-150769","volume":"6","author":"P Tagliaferro","year":"2016","unstructured":"Tagliaferro, P. & Burke, R. E. Retrograde axonal degeneration in Parkinson disease. J. Parkinsons. Dis. 6, 1\u201315 (2016).","journal-title":"J. Parkinsons. Dis."},{"key":"542_CR75","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1002\/mds.27823","volume":"34","author":"YC Wong","year":"2019","unstructured":"Wong, Y. C. et al. Neuronal vulnerability in Parkinson disease: should the focus be on axons and synaptic terminals? Mov. Disord. 34, 1406\u20131422 (2019).","journal-title":"Mov. Disord."},{"key":"542_CR76","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/S0006-8993(98)00198-X","volume":"791","author":"M Takada","year":"1998","unstructured":"Takada, M., Tokuno, H., Nambu, A. & Inase, M. Corticostriatal input zones from the supplementary motor area overlap those from the contra- rather than ipsilateral primary motor cortex. Brain Res. 791, 335\u2013340 (1998).","journal-title":"Brain Res."},{"key":"542_CR77","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1152\/jn.2002.88.4.1830","volume":"88","author":"A Nambu","year":"2002","unstructured":"Nambu, A., Kaneda, K., Tokuno, H. & Takada, M. Organization of corticostriatal motor inputs in monkey putamen. J. Neurophysiol. 88, 1830\u20131842 (2002).","journal-title":"J. Neurophysiol."},{"key":"542_CR78","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.brainresrev.2004.09.008","volume":"48","author":"P Romanelli","year":"2005","unstructured":"Romanelli, P., Esposito, V., Schaal, D. W. & Heit, G. Somatotopy in the basal ganglia: experimental and clinical evidence for segregated sensorimotor channels. Brain Res. Rev. 48, 112\u2013128 (2005).","journal-title":"Brain Res. Rev."},{"key":"542_CR79","doi-asserted-by":"publisher","first-page":"1116","DOI":"10.1016\/j.neuron.2018.07.028","volume":"99","author":"G Foffani","year":"2018","unstructured":"Foffani, G. & Obeso, J. A. A cortical pathogenic theory of Parkinson\u2019s disease. Neuron 99, 1116\u20131128 (2018). This conceptual work turns the postulated pathogenesis of Parkinson disease upside down, proposing that corticostriatal activity may act as a somatotopic \u2018stressor\u2019 for nigrostriatal neurons.","journal-title":"Neuron"},{"key":"542_CR80","doi-asserted-by":"crossref","unstructured":"Pineda-pardo, J. A., Sanchez-Ferro, A., Monje, M. H. G., Pavese, N. & Obeso, J. A. Onset pattern of nigrostriatal denervation in early Parkinson\u2019s disease. Brain (2021).","DOI":"10.1093\/brain\/awab378"},{"key":"542_CR81","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1001\/archneur.63.4.584","volume":"63","author":"S Greffard","year":"2006","unstructured":"Greffard, S. et al. Motor score of the unified Parkinson disease rating scale as a good predictor of Lewy body-associated neuronal loss in the substantia nigra. Arch. Neurol. 63, 584\u2013588 (2006).","journal-title":"Arch. Neurol."},{"key":"542_CR82","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1002\/mds.870120607","volume":"12","author":"EG Gonera","year":"1997","unstructured":"Gonera, E. G., Van\u2019t Hof, M., Berger, H. J. C., Van Weel, C. & Horstink, M. W. I. M. Symptoms and duration of the prodromal phase in Parkinson\u2019s disease. Mov. Disord. 12, 871\u2013876 (1997).","journal-title":"Mov. Disord."},{"key":"542_CR83","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/S1474-4422(14)70287-X","volume":"14","author":"A Schrag","year":"2015","unstructured":"Schrag, A., Horsfall, L., Walters, K., Noyce, A. & Petersen, I. Prediagnostic presentations of Parkinson\u2019s disease in primary care: a case-control study. Lancet Neurol. 14, 57\u201364 (2015).","journal-title":"Lancet Neurol."},{"key":"542_CR84","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1002\/ana.22284","volume":"69","author":"R de la Fuente-Fernandez","year":"2011","unstructured":"de la Fuente-Fernandez, R. et al. Age-specific progression of nigrostriatal dysfunction in Parkinson\u2019s disease. Ann. Neurol. 69, 803\u2013810 (2011).","journal-title":"Ann. Neurol."},{"key":"542_CR85","doi-asserted-by":"publisher","first-page":"e76595","DOI":"10.1371\/journal.pone.0076595","volume":"8","author":"L Kuramoto","year":"2013","unstructured":"Kuramoto, L. et al. The nature of progression in Parkinson\u2019s disease: an application of non-linear, multivariate, longitudinal random effects modelling. PLoS One 8, e76595 (2013).","journal-title":"PLoS One"},{"issue":"Suppl. 3","key":"542_CR86","doi-asserted-by":"publisher","first-page":"S548","DOI":"10.1002\/mds.22062","volume":"23","author":"JA Obeso","year":"2008","unstructured":"Obeso, J. A. et al. Functional organization of the basal ganglia: therapeutic implications for Parkinson\u2019s disease. Mov. Disord. 23 (Suppl. 3), S548\u2013S559 (2008).","journal-title":"Mov. Disord."},{"key":"542_CR87","doi-asserted-by":"publisher","first-page":"1861","DOI":"10.1111\/j.1471-4159.2008.05268.x","volume":"105","author":"XA Perez","year":"2008","unstructured":"Perez, X. A., Parameswaran, N., Huang, L. Z., O\u2019Leary, K. T. & Quik, M. Pre-synaptic dopaminergic compensation after moderate nigrostriatal damage in non-human primates. J. Neurochem. 105, 1861\u20131872 (2008).","journal-title":"J. Neurochem."},{"key":"542_CR88","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/S0165-6147(99)01343-7","volume":"20","author":"M Zoli","year":"1999","unstructured":"Zoli, M. et al. Volume transmission in the CNS and its relevance for neuropsychopharmacology. Trends Pharmacol. Sci. 20, 142\u2013150 (1999).","journal-title":"Trends Pharmacol. Sci."},{"key":"542_CR89","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1002\/mds.25135","volume":"27","author":"JP Bolam","year":"2012","unstructured":"Bolam, J. P. & Pissadaki, E. K. Living on the edge with too many mouths to feed: why dopamine neurons die. Mov. Disord. 27, 1478\u20131483 (2012).","journal-title":"Mov. Disord."},{"key":"542_CR90","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1523\/JNEUROSCI.4029-08.2009","volume":"29","author":"W Matsuda","year":"2009","unstructured":"Matsuda, W. et al. Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal arborizations in the neostriatum. J. Neurosci. 29, 444\u2013453 (2009).","journal-title":"J. Neurosci."},{"key":"542_CR91","doi-asserted-by":"publisher","first-page":"1224","DOI":"10.1046\/j.1471-4159.2003.02104.x","volume":"87","author":"BP Bergstrom","year":"2003","unstructured":"Bergstrom, B. P. & Garris, P. A. \u2018Passive stabilization\u2019 of striatal extracellular dopamine across the lesion spectrum encompassing the presymptomatic phase of Parkinson\u2019s disease: a voltammetric study in the 6-OHDA-lesioned rat. J. Neurochem. 87, 1224\u20131236 (2003).","journal-title":"J. Neurochem."},{"key":"542_CR92","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1007\/978-3-7091-0932-8_24","volume":"970","author":"B Picconi","year":"2012","unstructured":"Picconi, B., Piccoli, G. & Calabresi, P. Synaptic dysfunction in Parkinson\u2019s disease. Adv. Exp. Med. Biol. 970, 553\u2013572 (2012).","journal-title":"Adv. Exp. Med. Biol."},{"issue":"Suppl. 3","key":"542_CR93","doi-asserted-by":"publisher","first-page":"S421","DOI":"10.1016\/S1353-8020(08)70041-5","volume":"13","author":"AJ Stoessl","year":"2007","unstructured":"Stoessl, A. J. Positron emission tomography in premotor Parkinson\u2019s disease. Parkinsonims Relat. Disord. 13 (Suppl. 3), S421\u2013S424 (2007).","journal-title":"Parkinsonims Relat. Disord."},{"key":"542_CR94","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/S1474-4422(17)30056-X","volume":"16","author":"DJ Wile","year":"2017","unstructured":"Wile, D. J. et al. Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies. Lancet Neurol. 16, 351\u2013359 (2017).","journal-title":"Lancet Neurol."},{"key":"542_CR95","doi-asserted-by":"publisher","first-page":"6853","DOI":"10.1523\/JNEUROSCI.21-17-06853.2001","volume":"21","author":"E Bezard","year":"2001","unstructured":"Bezard, E. et al. Relationship between the appearance of symptoms and the level of nigrostriatal degeneration in a progressive 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson\u2019s disease. J. Neurosci. 21, 6853\u20136861 (2001).","journal-title":"J. Neurosci."},{"key":"542_CR96","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.nbd.2012.05.018","volume":"48","author":"J Blesa","year":"2012","unstructured":"Blesa, J. et al. The nigrostriatal system in the presymptomatic and symptomatic stages in the MPTP monkey model: a PET, histological and biochemical study. Neurobiol. Dis. 48, 79\u201391 (2012).","journal-title":"Neurobiol. Dis."},{"key":"542_CR97","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.tins.2003.12.006","volume":"27","author":"JA Obeso","year":"2004","unstructured":"Obeso, J. A., Rodriguez-Oroz, M. C., Lanciego, J. L. & Diaz, M. R. How does Parkinson\u2019s disease begin? The role of compensatory mechanisms. Trends Neurosci. 27, 125\u2013128 (2004).","journal-title":"Trends Neurosci."},{"issue":"Suppl. 2","key":"542_CR98","first-page":"S30","volume":"64","author":"JA Obeso","year":"2008","unstructured":"Obeso, J. A. et al. The basal ganglia in Parkinson\u2019s disease: current concepts and unexplained observations. Ann. Neurol. 64 (Suppl. 2), S30\u2013S46 (2008).","journal-title":"Ann. Neurol."},{"key":"542_CR99","unstructured":"Bezard, E., Boraud, T., Bioulac, B. & Gross, C. E. in The Basal Ganglia VI 107\u2013116 (Kluwer Academic, 2002)."},{"key":"542_CR100","doi-asserted-by":"publisher","first-page":"3408","DOI":"10.1093\/brain\/awaa274","volume":"143","author":"C Ammann","year":"2020","unstructured":"Ammann, C. et al. Cortical disinhibition in Parkinson\u2019s disease. Brain 143, 3408\u20133421 (2020).","journal-title":"Brain"},{"key":"542_CR101","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1523\/JNEUROSCI.4188-09.2010","volume":"30","author":"CC Tang","year":"2011","unstructured":"Tang, C. C., Poston, K. L., Dhawan, V. & Eidelberg, D. Abnormalities in metabolic network activity precede the onset of motor symptoms in Parkinson\u2019s disease. J. Neurosci. 30, 1049\u20131056 (2011).","journal-title":"J. Neurosci."},{"key":"542_CR102","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1385\/MN:28:3:209","volume":"28","author":"W Meissner","year":"2003","unstructured":"Meissner, W. et al. Time-course of nigrostriatal degeneration in a progressive MPTP-lesioned macaque model of Parkinson\u2019s disease. Mol. Neurobiol. 28, 209\u2013218 (2003).","journal-title":"Mol. Neurobiol."},{"key":"542_CR103","doi-asserted-by":"publisher","first-page":"1834","DOI":"10.1093\/brain\/awm086","volume":"130","author":"C Huang","year":"2007","unstructured":"Huang, C. et al. Changes in network activity with the progression of Parkinson\u2019s disease. Brain 130, 1834\u20131846 (2007).","journal-title":"Brain"},{"key":"542_CR104","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1002\/mds.27960","volume":"35","author":"KA Schindlbeck","year":"2019","unstructured":"Schindlbeck, K. A. et al. Metabolic network abnormalities in drug-na\u00efve Parkinson\u2019s disease. Mov. Disord. 35, 587\u2013594 (2019).","journal-title":"Mov. Disord."},{"key":"542_CR105","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1093\/brain\/114.3.1363","volume":"114","author":"JH Xuereb","year":"1991","unstructured":"Xuereb, J. H. et al. Nerve cell loss in the thalamus in Alzheimer\u2019s disease and Parkinson\u2019s disease. Brain 114, 1363\u20131379 (1991).","journal-title":"Brain"},{"key":"542_CR106","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.brainresbull.2008.08.014","volume":"78","author":"D Brooks","year":"2009","unstructured":"Brooks, D. & Halliday, G. M. Intralaminar nuclei of the thalamus in Lewy body diseases. Brain Res. Bull. 78, 97\u2013104 (2009).","journal-title":"Brain Res. Bull."},{"key":"542_CR107","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1002\/1531-8249(200003)47:3<345::AID-ANA10>3.0.CO;2-V","volume":"47","author":"JM Henderson","year":"2000","unstructured":"Henderson, J. M., Carpenter, K., Cartwright, H. & Halliday, G. M. Degeneration of the centre median-parafascicular complex in Parkinson\u2019s disease. Ann. Neurol. 47, 345\u2013352 (2000).","journal-title":"Ann. Neurol."},{"key":"542_CR108","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s00429-013-0507-9","volume":"219","author":"RM Villalba","year":"2014","unstructured":"Villalba, R. M., Wichmann, T. & Smith, Y. Neuronal loss in the caudal intralaminar thalamic nuclei in a primate model of Parkinson\u2019s disease. Brain Struct. Funct. 219, 381\u2013394 (2014).","journal-title":"Brain Struct. Funct."},{"key":"542_CR109","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/mds.27921","volume":"35","author":"MHG Monje","year":"2020","unstructured":"Monje, M. H. G., Blesa, J., Garc\u00eda-Cabezas, M. \u00c1., Obeso, J. A. & Cavada, C. Changes in thalamic dopamine innervation in a progressive Parkinson\u2019s disease model in monkeys. Mov. Disord. 35, 419\u2013430 (2020).","journal-title":"Mov. Disord."},{"issue":"Suppl. 3","key":"542_CR110","doi-asserted-by":"publisher","first-page":"S152","DOI":"10.1016\/S1353-8020(09)70804-1","volume":"15","author":"GM Halliday","year":"2009","unstructured":"Halliday, G. M. Thalamic changes in Parkinson\u2019s disease. Parkinsonism Relat. Disord. 15 (Suppl. 3), S152\u2013S155 (2009).","journal-title":"Parkinsonism Relat. Disord."},{"issue":"Suppl. 10","key":"542_CR111","doi-asserted-by":"publisher","first-page":"S8","DOI":"10.1016\/S1471-1931(00)00028-8","volume":"23","author":"JA Obeso","year":"2000","unstructured":"Obeso, J. A. et al. Pathophysiology of the basal ganglia in Parkinson\u2019s disease. Trends Neurosci. 23 (Suppl. 10), S8\u2013S19 (2000).","journal-title":"Trends Neurosci."},{"key":"542_CR112","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1093\/brain\/123.7.1410","volume":"123","author":"JM Henderson","year":"2000","unstructured":"Henderson, J. M., Carpenter, K., Cartwright, H. & Halliday, G. M. Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson\u2019s disease: clinical and therapeutic implications. Brain 123, 1410\u20131421 (2000).","journal-title":"Brain"},{"key":"542_CR113","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1016\/S1474-4422(16)30048-5","volume":"15","author":"J Blesa","year":"2016","unstructured":"Blesa, J., Trigo-Damas, I. & Obeso, J. A. Parkinson\u2019s disease and thalamus: facts and fancy. Lancet Neurol. 15, e2 (2016).","journal-title":"Lancet Neurol."},{"key":"542_CR114","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3389\/fnsys.2014.00005","volume":"8","author":"Y Smith","year":"2014","unstructured":"Smith, Y. et al. The thalamostriatal system in normal and diseased states. Front. Syst. Neurosci. 8, 5 (2014).","journal-title":"Front. Syst. Neurosci."},{"key":"542_CR115","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1093\/brain\/aws360","volume":"136","author":"T Wu","year":"2013","unstructured":"Wu, T. & Hallett, M. The cerebellum in Parkinson\u2019s disease. Brain 136, 696\u2013709 (2013).","journal-title":"Brain"},{"key":"542_CR116","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.neuroscience.2009.12.036","volume":"166","author":"S Sen","year":"2010","unstructured":"Sen, S., Kawaguchi, A., Truong, Y., Lewis, M. M. & Huang, X. Dynamic changes in cerebello-thalamo-cortical motor circuitry during progression of Parkinson\u2019s disease. Neuroscience 166, 712\u2013719 (2010).","journal-title":"Neuroscience"},{"key":"542_CR117","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.neuroimage.2010.11.074","volume":"55","author":"T Wu","year":"2011","unstructured":"Wu, T. et al. Effective connectivity of brain networks during self-initiated movement in Parkinson\u2019s disease. Neuroimage 55, 204\u2013215 (2011).","journal-title":"Neuroimage"},{"key":"542_CR118","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1093\/brain\/124.3.558","volume":"124","author":"B Haslinger","year":"2001","unstructured":"Haslinger, B. et al. Event-related functional magnetic resonance imaging in Parkinson\u2019s disease before and after levodopa. Brain 124, 558\u2013570 (2001).","journal-title":"Brain"},{"key":"542_CR119","doi-asserted-by":"publisher","first-page":"2187","DOI":"10.1111\/j.1460-9568.2009.06753.x","volume":"29","author":"SJ Palmer","year":"2009","unstructured":"Palmer, S. J., Ng, B., Abugharbieh, R., Eigenraam, L. & McKeown, M. J. Motor reserve and novel area recruitment: amplitude and spatial characteristics of compensation in Parkinson\u2019s disease. Eur. J. Neurosci. 29, 2187\u20132196 (2009).","journal-title":"Eur. J. Neurosci."},{"key":"542_CR120","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1212\/WNL.0b013e318253d5dd","volume":"78","author":"M Kojovic","year":"2012","unstructured":"Kojovic, M. et al. Functional reorganization of sensorimotor cortex in early Parkinson disease. Neurology 78, 1441\u20131448 (2012).","journal-title":"Neurology"},{"key":"542_CR121","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1016\/j.clinph.2011.06.034","volume":"123","author":"A Kishore","year":"2012","unstructured":"Kishore, A., Joseph, T., Velayudhan, B., Popa, T. & Meunier, S. Early, severe and bilateral loss of LTP and LTD-like plasticity in motor cortex (M1) in de novo Parkinson\u2019s disease. Clin. Neurophysiol. 123, 822\u2013828 (2012).","journal-title":"Clin. Neurophysiol."},{"key":"542_CR122","doi-asserted-by":"crossref","unstructured":"Kojovic, M. et al. Transcranial magnetic stimulation follow-up study in early Parkinson\u2019s disease: a decline in compensation with disease progression? 30, 1098\u20131106 (2015).","DOI":"10.1002\/mds.26167"},{"key":"542_CR123","doi-asserted-by":"publisher","first-page":"1746","DOI":"10.1212\/WNL.0b013e3182919029","volume":"80","author":"Z Ni","year":"2013","unstructured":"Ni, Z., Bahl, N., Gunraj, C. A., Mazzella, F. & Chen, R. Increased motor cortical facilitation and decreased inhibition in Parkinson disease. Neurology 80, 1746\u20131753 (2013).","journal-title":"Neurology"},{"key":"542_CR124","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/B978-0-444-64142-7.00047-3","volume":"161","author":"K Udupa","year":"2019","unstructured":"Udupa, K. & Chen, R. Motor cortical circuits in Parkinson disease and dystonia. Handb. Clin. Neurol. 161, 167\u2013186 (2019).","journal-title":"Handb. Clin. Neurol."},{"key":"542_CR125","doi-asserted-by":"publisher","first-page":"1554","DOI":"10.1002\/mds.28558","volume":"36","author":"J Ueda","year":"2021","unstructured":"Ueda, J. et al. Perampanel inhibits \u03b1-synuclein transmission in Parkinson\u2019s disease models. Mov. Disord. 36, 1554\u20131564 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR126","doi-asserted-by":"publisher","first-page":"1487","DOI":"10.1002\/mds.28618","volume":"36","author":"DJ Surmeier","year":"2021","unstructured":"Surmeier, D. J. Beyond just connectivity \u2014 neuronal activity drives \u03b1-synuclein pathology. Mov. Disord. 36, 1487\u20131488 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR127","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1212\/WNL.58.10.1501","volume":"58","author":"AG Schuurman","year":"2002","unstructured":"Schuurman, A. G. et al. Increased risk of Parkinson\u2019s disease after depression: a retrospective cohort study. Neurology 58, 1501\u20131504 (2002).","journal-title":"Neurology"},{"key":"542_CR128","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.1212\/WNL.0000000000001684","volume":"84","author":"H Gustafsson","year":"2015","unstructured":"Gustafsson, H., Nordstr\u00f6m, A. & Nordstr\u00f6m, P. Depression and subsequent risk of Parkinson disease: a nationwide cohort study. Neurology 84, 2422\u20132429 (2015).","journal-title":"Neurology"},{"key":"542_CR129","doi-asserted-by":"publisher","first-page":"475","DOI":"10.3389\/fimmu.2016.00475","volume":"7","author":"F Imamura","year":"2016","unstructured":"Imamura, F. & Hasegawa-Ishii, S. Environmental toxicants-induced immune responses in the olfactory mucosa. Front. Immunol. 7, 475 (2016).","journal-title":"Front. Immunol."},{"key":"542_CR130","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.nbd.2016.12.013","volume":"109","author":"NL Rey","year":"2018","unstructured":"Rey, N. L., Wesson, D. W. & Brundin, P. The olfactory bulb as the entry site for prion-like propagation in neurodegenerative diseases. Neurobiol. Dis. 109, 226\u2013248 (2018).","journal-title":"Neurobiol. Dis."},{"key":"542_CR131","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/ki.2011.189","volume":"80","author":"BN Landis","year":"2011","unstructured":"Landis, B. N. et al. Olfactory function improves following hemodialysis. Kidney Int. 80, 886\u2013893 (2011).","journal-title":"Kidney Int."},{"key":"542_CR132","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/ki.2011.219","volume":"80","author":"AS Bomback","year":"2011","unstructured":"Bomback, A. S. & Raff, A. C. Olfactory function in dialysis patients: a potential key to understanding the uremic state. Kidney Int. 80, 803\u2013805 (2011).","journal-title":"Kidney Int."},{"key":"542_CR133","doi-asserted-by":"publisher","first-page":"934","DOI":"10.2337\/diacare.16.6.934","volume":"16","author":"JP Le Floch","year":"1993","unstructured":"Le Floch, J. P. et al. Smell dysfunction and related factors in diabetic patients. Diabetes Care 16, 934\u2013937 (1993).","journal-title":"Diabetes Care"},{"key":"542_CR134","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1111\/dme.13542","volume":"35","author":"H Zaghloul","year":"2018","unstructured":"Zaghloul, H., Pallayova, M., Al-Nuaimi, O., Hovis, K. R. & Taheri, S. Association between diabetes mellitus and olfactory dysfunction: current perspectives and future directions. Diabet. Med. 35, 41\u201352 (2018).","journal-title":"Diabet. Med."},{"key":"542_CR135","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1111\/bpa.12220","volume":"25","author":"GC DeLuca","year":"2015","unstructured":"DeLuca, G. C., Yates, R. L., Beale, H. & Morrow, S. A. Cognitive impairment in multiple sclerosis: clinical, radiologic and pathologic insights. Brain Pathol. 25, 79\u201398 (2015).","journal-title":"Brain Pathol."},{"key":"542_CR136","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1111\/ene.12891","volume":"23","author":"\u00d6 Yaldizli","year":"2016","unstructured":"Yaldizli, \u00d6. et al. The association between olfactory bulb volume, cognitive dysfunction, physical disability and depression in multiple sclerosis. Eur. J. Neurol. 23, 510\u2013519 (2016).","journal-title":"Eur. J. Neurol."},{"key":"542_CR137","doi-asserted-by":"publisher","first-page":"1890","DOI":"10.1007\/s00415-015-7787-3","volume":"262","author":"LJ Zhang","year":"2015","unstructured":"Zhang, L. J. et al. Olfactory dysfunction in neuromyelitis optica spectrum disorders. J. Neurol. 262, 1890\u20131898 (2015).","journal-title":"J. Neurol."},{"key":"542_CR138","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1002\/art.24491","volume":"60","author":"N Shoenfeld","year":"2009","unstructured":"Shoenfeld, N. et al. The sense of smell in systemic lupus erythematosus. Arthritis Rheum. 60, 1484\u20131487 (2009).","journal-title":"Arthritis Rheum."},{"key":"542_CR139","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1080\/03610730802070001","volume":"34","author":"RS Wilson","year":"2008","unstructured":"Wilson, R. S., Arnold, S. E., Buchman, A. S., Tang, Y. & Bennett, D. A. Odor identification and progression of Parkinsonian signs in older persons. Exp. Aging Res. 34, 173\u2013187 (2008).","journal-title":"Exp. Aging Res."},{"key":"542_CR140","doi-asserted-by":"publisher","first-page":"2062","DOI":"10.1002\/mds.21076","volume":"21","author":"GW Ross","year":"2006","unstructured":"Ross, G. W. et al. Association of olfactory dysfunction with incidental Lewy bodies. Mov. Disord. 21, 2062\u20132067 (2006).","journal-title":"Mov. Disord."},{"key":"542_CR141","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1002\/ana.20160","volume":"56","author":"MM Ponsen","year":"2004","unstructured":"Ponsen, M. M. et al. Idiopathic hyposmia as a preclinical sign of Parkinson\u2019s disease. Ann. Neurol. 56, 173\u2013181 (2004).","journal-title":"Ann. Neurol."},{"key":"542_CR142","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1002\/mds.21413","volume":"22","author":"A Haehner","year":"2007","unstructured":"Haehner, A. et al. Olfactory loss may be a first sign of idiopathic Parkinson\u2019s disease. Mov. Disord. 22, 839\u2013842 (2007).","journal-title":"Mov. Disord."},{"key":"542_CR143","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1002\/ana.21291","volume":"63","author":"GW Ross","year":"2008","unstructured":"Ross, G. W. et al. Association of olfactory dysfunction with risk for future Parkinson\u2019s disease. Ann. Neurol. 63, 167\u2013173 (2008).","journal-title":"Ann. Neurol."},{"key":"542_CR144","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1002\/mds.24985","volume":"27","author":"D Berg","year":"2012","unstructured":"Berg, D., Marek, K., Ross, G. W. & Poewe, W. Defining at-risk populations for Parkinson\u2019s disease: lessons from ongoing studies. Mov. Disord. 27, 656\u2013665 (2012).","journal-title":"Mov. Disord."},{"key":"542_CR145","doi-asserted-by":"publisher","first-page":"1441","DOI":"10.1212\/WNL.0000000000004382","volume":"89","author":"H Chen","year":"2017","unstructured":"Chen, H. et al. Olfaction and incident Parkinson disease in US white and black older adults. Neurology 89, 1441\u20131447 (2017).","journal-title":"Neurology"},{"key":"542_CR146","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1007\/s00415-018-9135-x","volume":"266","author":"A Haehner","year":"2019","unstructured":"Haehner, A., Masala, C., Walter, S., Reichmann, H. & Hummel, T. Incidence of Parkinson\u2019s disease in a large patient cohort with idiopathic smell and taste loss. J. Neurol. 266, 339\u2013345 (2019).","journal-title":"J. Neurol."},{"key":"542_CR147","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/j.parkreldis.2019.12.008","volume":"70","author":"P Mahlknecht","year":"2020","unstructured":"Mahlknecht, P. et al. Midbrain hyperechogenicity, hyposmia, mild parkinsonian signs and risk for incident Parkinson\u2019s disease over 10 years: a prospective population-based study. Parkinsonism Relat. Disord. 70, 51\u201354 (2020).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR148","doi-asserted-by":"publisher","first-page":"1060","DOI":"10.1002\/mds.22534","volume":"24","author":"MM Ponsen","year":"2009","unstructured":"Ponsen, M. M., Stoffers, D., Twisk, J. W. R., Wolters, E. C. & Berendse, H. W. Hyposmia and executive dysfunction as predictors of future Parkinson\u2019s disease: a prospective study. Mov. Disord. 24, 1060\u20131065 (2009).","journal-title":"Mov. Disord."},{"key":"542_CR149","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.parkreldis.2021.01.005","volume":"84","author":"JM Janssen Daalen","year":"2021","unstructured":"Janssen Daalen, J. M. et al. Towards subgroup-specific risk estimates: a meta-analysis of longitudinal studies on olfactory dysfunction and risk of Parkinson\u2019s disease. Parkinsonism Relat. Disord. 84, 155\u2013163 (2021).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR150","doi-asserted-by":"publisher","first-page":"2051","DOI":"10.1093\/brain\/awz111","volume":"142","author":"S-M Fereshtehnejad","year":"2019","unstructured":"Fereshtehnejad, S.-M. et al. Evolution of prodromal Parkinson\u2019s disease and dementia with Lewy bodies: a prospective study. Brain 142, 2051\u20132067 (2019).","journal-title":"Brain"},{"key":"542_CR151","doi-asserted-by":"publisher","first-page":"976","DOI":"10.1002\/acn3.594","volume":"5","author":"C Viguera","year":"2018","unstructured":"Viguera, C., Wang, J., Mosmiller, E., Cerezo, A. & Maragakis, N. J. Olfactory dysfunction in amyotrophic lateral sclerosis. Ann. Clin. Transl. Neurol. 5, 976\u2013981 (2018).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"542_CR152","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1017\/S1355617700000278","volume":"1","author":"S Nordin","year":"1995","unstructured":"Nordin, S., Paulsen, J. S. & Murphy, C. Sensory- and memory-mediated olfactory dysfunction in Huntington\u2019s disease. J. Int. Neuropsychol. Soc. 1, 281\u2013290 (1995).","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"542_CR153","doi-asserted-by":"publisher","first-page":"133","DOI":"10.3109\/00207459708988468","volume":"89","author":"PJ Moberg","year":"1997","unstructured":"Moberg, P. J. & Doty, R. L. Olfactory function in Huntington\u2019s disease patients and at-risk offspring. Int. J. Neurosci. 89, 133\u2013139 (1997).","journal-title":"Int. J. Neurosci."},{"key":"542_CR154","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.parkreldis.2018.04.028","volume":"53","author":"M Marek","year":"2018","unstructured":"Marek, M., Linnepe, S., Klein, C., Hummel, T. & Paus, S. High prevalence of olfactory dysfunction in cervical dystonia. Parkinsonism Relat. Disord. 53, 33\u201336 (2018).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR155","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/0361-9230(87)90129-8","volume":"18","author":"RL Doty","year":"1987","unstructured":"Doty, R. L., Reyes, P. F. & Gregor, T. Presence of both odor identification and detection deficits in Alzheimer\u2019s disease. Brain Res. Bull. 18, 597\u2013600 (1987).","journal-title":"Brain Res. Bull."},{"key":"542_CR156","doi-asserted-by":"publisher","first-page":"100956","DOI":"10.1016\/j.arr.2019.100956","volume":"55","author":"P Bathini","year":"2019","unstructured":"Bathini, P., Brai, E. & Auber, L. A. Olfactory dysfunction in the pathophysiological continuum of dementia. Ageing Res. Rev. 55, 100956 (2019).","journal-title":"Ageing Res. Rev."},{"key":"542_CR157","doi-asserted-by":"publisher","first-page":"e0231720","DOI":"10.1371\/journal.pone.0231720","volume":"15","author":"TG Beach","year":"2020","unstructured":"Beach, T. G. et al. Severe hyposmia distinguishes neuropathologically confirmed dementia with Lewy bodies from Alzheimer\u2019s disease dementia. PLoS One 15, e0231720 (2020).","journal-title":"PLoS One"},{"key":"542_CR158","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1017\/S1355617704106024","volume":"10","author":"PE Gilbert","year":"2004","unstructured":"Gilbert, P. E., Barr, P. J. & Murphy, C. Differences in olfactory and visual memory in patients with pathologically confirmed Alzheimer\u2019s disease and the Lewy body variant of Alzheimer\u2019s disease. J. Int. Neuropsychol. Soc. 10, 835\u2013842 (2004).","journal-title":"J. Int. Neuropsychol. Soc."},{"key":"542_CR159","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1212\/WNL.38.8.1237","volume":"38","author":"RL Doty","year":"1988","unstructured":"Doty, R. L., Deems, D. A. & Stellar, S. Olfactory dysfunction in parkinsonism: a general deficit unrelated to neurologic signs, disease stage, or disease duration. Neurology 38, 1237\u20131244 (1988).","journal-title":"Neurology"},{"key":"542_CR160","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.bandc.2016.01.004","volume":"104","author":"TL White","year":"2016","unstructured":"White, T. L., Sadikot, A. F. & Djordjevic, J. Metacognitive knowledge of olfactory dysfunction in Parkinson\u2019s disease. Brain Cogn. 104, 1\u20136 (2016).","journal-title":"Brain Cogn."},{"key":"542_CR161","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/nrneurol.2012.80","volume":"8","author":"RL Doty","year":"2012","unstructured":"Doty, R. L. Olfactory dysfunction in Parkinson disease. Nat. Rev. Neurol. 8, 329\u2013339 (2012). This review discusses the current understanding of olfactory dysfunction in PD and suggests that deficits in structures other than the olfactory bulb may contribute to olfactory loss.","journal-title":"Nat. Rev. Neurol."},{"key":"542_CR162","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1016\/j.parkreldis.2008.12.005","volume":"15","author":"A Haehner","year":"2009","unstructured":"Haehner, A. et al. Prevalence of smell loss in Parkinson\u2019s disease \u2014 a multicenter study. Parkinsonism Relat. Disord. 15, 490\u2013494 (2009).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR163","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1212\/01.wnl.0000336651.48596.c7","volume":"71","author":"D Verbaan","year":"2008","unstructured":"Verbaan, D. et al. Is olfactory impairment in Parkinson disease related to phenotypic or genotypic characteristics? Neurology 71, 1877\u20131882 (2008).","journal-title":"Neurology"},{"key":"542_CR164","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/0021-9681(75)90058-2","volume":"28","author":"KA Ansari","year":"1975","unstructured":"Ansari, K. A. & Johnson, A. Olfactory function in patients with Parkinson\u2019s disease. J. Chronic Dis. 28, 493\u2013497 (1975).","journal-title":"J. Chronic Dis."},{"key":"542_CR165","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1136\/jnnp-2017-316213","volume":"89","author":"T Simuni","year":"2018","unstructured":"Simuni, T. et al. Baseline prevalence and longitudinal evolution of non-motor symptoms in early Parkinson\u2019s disease: the PPMI cohort. J. Neurol. Neurosurg. Psychiatry 89, 78\u201388 (2018).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR166","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/mdc3.12220","volume":"3","author":"HA Shill","year":"2016","unstructured":"Shill, H. A. et al. Unawareness of hyposmia in elderly people with and without Parkinson\u2019s disease. Mov. Disord. Clin. Pract. 3, 43\u201347 (2016).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"542_CR167","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1002\/mds.26687","volume":"31","author":"M Rossi","year":"2016","unstructured":"Rossi, M. et al. Motor features in Parkinson\u2019s disease with normal olfactory function. Mov. Disord. 31, 1414\u20131417 (2016).","journal-title":"Mov. Disord."},{"key":"542_CR168","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.parkreldis.2017.02.017","volume":"38","author":"ME Domell\u00f6f","year":"2017","unstructured":"Domell\u00f6f, M. E., Lundin, K. F., Edstr\u00f6m, M. & Forsgren, L. Olfactory dysfunction and dementia in newly diagnosed patients with Parkinson\u2019s disease. Parkinsonism Relat. Disord. 38, 41\u201347 (2017).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR169","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1212\/WNL.0000000000001999","volume":"85","author":"DH Lee","year":"2015","unstructured":"Lee, D. H. et al. Is normosmic Parkinson disease a unique clinical phenotype? Neurology 85, 1270\u20131275 (2015).","journal-title":"Neurology"},{"key":"542_CR170","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1002\/mds.23782","volume":"26","author":"MF Damholdt","year":"2011","unstructured":"Damholdt, M. F., Borghammer, P., Larsen, L. & Ostergaard, K. Odor identification deficits identify Parkinson\u2019s disease patients with poor cognitive performance. Mov. Disord. 26, 2045\u20132050 (2011).","journal-title":"Mov. Disord."},{"key":"542_CR171","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1093\/brain\/awr321","volume":"135","author":"T Baba","year":"2012","unstructured":"Baba, T. et al. Severe olfactory dysfunction is a prodromal symptom of dementia associated with Parkinson\u2019s disease: a 3 year longitudinal study. Brain 135, 161\u2013169 (2012).","journal-title":"Brain"},{"key":"542_CR172","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/j.parkreldis.2016.02.013","volume":"25","author":"ME Fullard","year":"2016","unstructured":"Fullard, M. E. et al. Olfactory impairment predicts cognitive decline in early Parkinson\u2019s disease. Parkinsonism Relat. Disord. 25, 45\u201351 (2016).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR173","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/S1474-4422(16)30328-3","volume":"16","author":"A Schrag","year":"2017","unstructured":"Schrag, A., Siddiqui, U. F., Anastasiou, Z., Weintraub, D. & Schott, J. M. Clinical variables and biomarkers in prediction of cognitive impairment in patients with newly diagnosed Parkinson\u2019s disease: a cohort study. Lancet Neurol. 16, 66\u201375 (2017).","journal-title":"Lancet Neurol."},{"key":"542_CR174","doi-asserted-by":"publisher","first-page":"1747","DOI":"10.1093\/brain\/awq079","volume":"133","author":"NI Bohnen","year":"2010","unstructured":"Bohnen, N. I. et al. Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson\u2019s disease. Brain 133, 1747\u20131754 (2010).","journal-title":"Brain"},{"key":"542_CR175","doi-asserted-by":"publisher","first-page":"E2045","DOI":"10.1212\/WNL.0000000000006576","volume":"91","author":"D B\u00e4ckstr\u00f6m","year":"2018","unstructured":"B\u00e4ckstr\u00f6m, D. et al. Early predictors of mortality in parkinsonism and Parkinson disease: a population-based study. Neurology 91, E2045\u2013E2056 (2018).","journal-title":"Neurology"},{"key":"542_CR176","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1136\/jnnp.50.1.88","volume":"50","author":"NP Quinn","year":"1987","unstructured":"Quinn, N. P., Rossor, M. N. & Marsden, C. D. Olfactory threshold in Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry 50, 88\u201389 (1987).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR177","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1136\/jnnp.55.2.138","volume":"55","author":"RL Doty","year":"1992","unstructured":"Doty, R. L., Stern, M. B., Pfeiffer, C., Gollomp, S. M. & Hurtig, H. I. Bilateral olfactory dysfunction in early stage treated and untreated idiopathic Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry 55, 138\u2013142 (1992).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR178","doi-asserted-by":"publisher","first-page":"1054","DOI":"10.1016\/S0140-6736(95)90797-1","volume":"345","author":"J Lehrner","year":"1995","unstructured":"Lehrner, J., Br\u00fccke, T., Kryspin-Exner, I., Asenbaum, S. & Podreka, I. Impaired olfactory function in Parkinson\u2019s disease. Lancet 345, 1054\u20131055 (1995).","journal-title":"Lancet"},{"key":"542_CR179","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1002\/1531-8257(200101)16:1<41::AID-MDS1017>3.0.CO;2-M","volume":"16","author":"G Tissingh","year":"2001","unstructured":"Tissingh, G. et al. Loss of olfaction in de novo and treated Parkinson\u2019s disease: possible implications for early diagnosis. Mov. Disord. 16, 41\u201346 (2001).","journal-title":"Mov. Disord."},{"key":"542_CR180","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1212\/01.WNL.0000161874.52302.5D","volume":"64","author":"A Siderowf","year":"2005","unstructured":"Siderowf, A. et al. [99mTc]TRODAT-1 SPECT imaging correlates with odor identification in early Parkinson disease. Neurology 64, 1716\u20131720 (2005).","journal-title":"Neurology"},{"key":"542_CR181","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1016\/j.neulet.2010.09.044","volume":"486","author":"T Meusel","year":"2010","unstructured":"Meusel, T., Westermann, B., Fuhr, P., Hummel, T. & Welge-Lussen, A. The course of olfactory deficits in patients with Parkinson\u2019s disease \u2014 a study based on psychophysical and electrophysiological measures. Neurosci. Lett. 486, 166\u2013170 (2010).","journal-title":"Neurosci. Lett."},{"key":"542_CR182","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1093\/qjmed\/hcq142","volume":"103","author":"J Deeb","year":"2010","unstructured":"Deeb, J. et al. A basic smell test is as sensitive as a dopamine transporter scan: comparison of olfaction, taste and DaTSCAN in the diagnosis of Parkinson\u2019s disease. QJM 103, 941\u2013952 (2010).","journal-title":"QJM"},{"key":"542_CR183","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.jns.2011.06.020","volume":"310","author":"HW Berendse","year":"2011","unstructured":"Berendse, H. W., Roos, D. S., Raijmakers, P. & Doty, R. L. Motor and non-motor correlates of olfactory dysfunction in Parkinson\u2019s disease. J. Neurol. Sci. 310, 21\u201324 (2011).","journal-title":"J. Neurol. Sci."},{"key":"542_CR184","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.parkreldis.2017.05.005","volume":"41","author":"A Campabadal","year":"2017","unstructured":"Campabadal, A. et al. Brain correlates of progressive olfactory loss in Parkinson\u2019s disease. Parkinsonism Relat. Disord. 41, 44\u201350 (2017).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR185","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1001\/jamaneurol.2014.2950","volume":"72","author":"M Beavan","year":"2015","unstructured":"Beavan, M. et al. Evolution of prodromal clinical markers of Parkinson disease in a GBA mutation-positive cohort. JAMA Neurol. 72, 201\u2013208 (2015).","journal-title":"JAMA Neurol."},{"key":"542_CR186","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1002\/ana.410320116","volume":"32","author":"RL Doty","year":"1992","unstructured":"Doty, R. L., Singh, A., Tetrud, J. & Langston, J. W. Lack of major olfactory dysfunction in MPTP-induced parkinsonism. Ann. Neurol. 32, 97\u2013100 (1992).","journal-title":"Ann. Neurol."},{"key":"542_CR187","doi-asserted-by":"publisher","first-page":"1574","DOI":"10.1007\/s00415-008-0993-5","volume":"255","author":"S Kr\u00fcger","year":"2008","unstructured":"Kr\u00fcger, S., Haehner, A., Thiem, C. & Hummel, T. Neuroleptic-induced parkinsonism is associated with olfactory dysfunction. J. Neurol. 255, 1574\u20131579 (2008).","journal-title":"J. Neurol."},{"key":"542_CR188","doi-asserted-by":"publisher","first-page":"1250","DOI":"10.1136\/jnnp.2007.121285","volume":"78","author":"HL Phil","year":"2007","unstructured":"Phil, H. L., Seung, H. Y., Seok, W. Y. & Yun, J. K. Odour identification test and its relation to cardiac 123I-metaiodobenzylguanidine in patients with drug induced parkinsonism. J. Neurol. Neurosurg. Psychiatry 78, 1250\u20131252 (2007).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR189","doi-asserted-by":"publisher","first-page":"1882","DOI":"10.1007\/s00415-010-5631-3","volume":"257","author":"T Bovi","year":"2010","unstructured":"Bovi, T. et al. The status of olfactory function and the striatal dopaminergic system in drug-induced parkinsonism. J. Neurol. 257, 1882\u20131889 (2010).","journal-title":"J. Neurol."},{"key":"542_CR190","doi-asserted-by":"publisher","first-page":"169","DOI":"10.3233\/JPD-130299","volume":"4","author":"JF Morley","year":"2014","unstructured":"Morley, J. F. & Duda, J. E. Use of hyposmia and other non-motor symptoms to distinguish between drug-induced Parkinsonism and Parkinson\u2019s disease. J. Parkinsons Dis. 4, 169\u2013173 (2014).","journal-title":"J. Parkinsons Dis."},{"key":"542_CR191","doi-asserted-by":"publisher","first-page":"1424","DOI":"10.1212\/WNL.49.5.1424","volume":"49","author":"S Barz","year":"1997","unstructured":"Barz, S. et al. Chemosensory event-related potentials in response to trigeminal and olfactory stimulation in idiopathic Parkinson\u2019s disease. Neurology 49, 1424\u20131431 (1997).","journal-title":"Neurology"},{"key":"542_CR192","first-page":"99","volume":"13","author":"J Roth","year":"1998","unstructured":"Roth, J., Radil, T., Ruzicka, E., Jech, R. & Tichy, J. Apomorphine does not influence olfactory thresholds in Parkinson\u2019s disease. Funct. Neurol. 13, 99\u2013103 (1998).","journal-title":"Funct. Neurol."},{"key":"542_CR193","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1136\/jnnp.62.5.436","volume":"62","author":"CH Hawkes","year":"1997","unstructured":"Hawkes, C. H., Shephard, B. C. & Daniel, S. E. Olfactory dysfunction in Parkinson\u2019s disease. J. Neurol. Neurosurg. Psychiatry 62, 436\u2013446 (1997).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR194","doi-asserted-by":"publisher","first-page":"667","DOI":"10.1002\/ana.410320510","volume":"32","author":"DC German","year":"1992","unstructured":"German, D. C. et al. Disease-specific patterns of locus coeruleus cell loss. Ann. Neurol. 32, 667\u2013676 (1992).","journal-title":"Ann. Neurol."},{"key":"542_CR195","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1002\/mds.870100309","volume":"10","author":"RK Pearce","year":"1995","unstructured":"Pearce, R. K., Hawkes, C. H. & Daniel, S. E. The anterior olfactory nucleus in Parkinson\u2019s disease. Mov. Disord. 10, 283\u2013287 (1995).","journal-title":"Mov. Disord."},{"key":"542_CR196","first-page":"80","volume":"35","author":"E Bertrand","year":"1997","unstructured":"Bertrand, E., Lechowicz, W., Szpak, G. M. & Dymecki, J. Qualitative and quantitative analysis of locus coeruleus neurons in Parkinson\u2019s disease. Folia Neuropathol. 35, 80\u201386 (1997).","journal-title":"Folia Neuropathol."},{"key":"542_CR197","doi-asserted-by":"publisher","first-page":"2431","DOI":"10.1093\/brain\/awf251","volume":"125","author":"AJ Harding","year":"2002","unstructured":"Harding, A. J., Stimson, E., Henderson, J. M. & Halliday, G. M. Clinical correlates of selective pathology in the amygdala of patients with Parkinson\u2019s disease. Brain 125, 2431\u20132445 (2002).","journal-title":"Brain"},{"key":"542_CR198","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s00401-014-1261-7","volume":"127","author":"J Attems","year":"2014","unstructured":"Attems, J., Walker, L. & Jellinger, K. A. Olfactory bulb involvement in neurodegenerative diseases. Acta Neuropathol. 127, 459\u2013475 (2014).","journal-title":"Acta Neuropathol."},{"key":"542_CR199","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1006\/exnr.1999.7228","volume":"160","author":"JE Duda","year":"1999","unstructured":"Duda, J. E., Shah, U., Arnold, S. E., Lee, V. M. & Trojanowski, J. Q. The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases. Exp. Neurol. 160, 515\u2013522 (1999).","journal-title":"Exp. Neurol."},{"key":"542_CR200","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1002\/mds.22464","volume":"24","author":"M Witt","year":"2009","unstructured":"Witt, M. et al. Biopsies of olfactory epithelium in patients with Parkinson\u2019s disease. Mov. Disord. 24, 906\u2013914 (2009).","journal-title":"Mov. Disord."},{"key":"542_CR201","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1002\/mds.26463","volume":"31","author":"Y Saito","year":"2016","unstructured":"Saito, Y. et al. Lewy body pathology involves the olfactory cells in Parkinson\u2019s disease and related disorders. Mov. Disord. 31, 135\u2013138 (2016).","journal-title":"Mov. Disord."},{"key":"542_CR202","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/j.1440-1789.2012.01329.x","volume":"33","author":"S Funabe","year":"2013","unstructured":"Funabe, S. et al. Neuropathologic analysis of Lewy-related \u03b1-synucleinopathy in olfactory mucosa. Neuropathology 33, 47\u201358 (2013).","journal-title":"Neuropathology"},{"key":"542_CR203","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/s41593-020-0587-9","volume":"23","author":"MA Durante","year":"2020","unstructured":"Durante, M. A. et al. Single-cell analysis of olfactory neurogenesis and differentiation in adult humans. Nat. Neurosci. 23, 323\u2013326 (2020).","journal-title":"Nat. Neurosci."},{"key":"542_CR204","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1007\/s00401-008-0450-7","volume":"117","author":"TG Beach","year":"2009","unstructured":"Beach, T. G. et al. Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders. Acta Neuropathol. 117, 169\u2013174 (2009).","journal-title":"Acta Neuropathol."},{"key":"542_CR205","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41572-018-0016-5","volume":"4","author":"Y Dauvilliers","year":"2018","unstructured":"Dauvilliers, Y. et al. REM sleep behaviour disorder. Nat. Rev. Dis. Primers 4, 20 (2018).","journal-title":"Nat. Rev. Dis. Primers"},{"key":"542_CR206","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1016\/S1474-4422(06)70476-8","volume":"5","author":"A Iranzo","year":"2006","unstructured":"Iranzo, A. et al. Rapid-eye-movement sleep behaviour disorder as an early marker for a neurodegenerative disorder: a descriptive study. Lancet Neurol. 5, 572\u2013577 (2006).","journal-title":"Lancet Neurol."},{"key":"542_CR207","doi-asserted-by":"publisher","first-page":"1296","DOI":"10.1212\/01.wnl.0000340980.19702.6e","volume":"72","author":"RB Postuma","year":"2009","unstructured":"Postuma, R. B. et al. Quantifying the risk of neurodegenerative disease in idiopathic REM sleep behavior disorder. Neurology 72, 1296\u20131300 (2009).","journal-title":"Neurology"},{"key":"542_CR208","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1093\/brain\/awz030","volume":"142","author":"RB Postuma","year":"2019","unstructured":"Postuma, R. B. et al. Risk and predictors of dementia and parkinsonism in idiopathic REM sleep behaviour disorder: a multicentre study. Brain 142, 744\u2013759 (2019).","journal-title":"Brain"},{"key":"542_CR209","doi-asserted-by":"publisher","first-page":"1959","DOI":"10.1093\/brain\/awx118","volume":"140","author":"S-M Fereshtehnejad","year":"2017","unstructured":"Fereshtehnejad, S.-M., Zeighami, Y., Dagher, A. & Postuma, R. B. Clinical criteria for subtyping Parkinson\u2019s disease: biomarkers and longitudinal progression. Brain 140, 1959\u20131976 (2017).","journal-title":"Brain"},{"key":"542_CR210","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1002\/mds.24996","volume":"27","author":"RB Postuma","year":"2012","unstructured":"Postuma, R. B. et al. Identifying prodromal Parkinson\u2019s disease: pre-motor disorders in Parkinson\u2019s disease. Mov. Disord. 27, 617\u2013626 (2012).","journal-title":"Mov. Disord."},{"key":"542_CR211","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/j.parkreldis.2018.05.020","volume":"55","author":"DR Shprecher","year":"2018","unstructured":"Shprecher, D. R. et al. Predicting alpha-synuclein pathology by REM sleep behavior disorder diagnosis. Parkinsonism Relat. Disord. 55, 92\u201396 (2018).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR212","doi-asserted-by":"publisher","first-page":"zsx197","DOI":"10.1093\/sleep\/zsx197","volume":"41","author":"J Haba-Rubio","year":"2018","unstructured":"Haba-Rubio, J. et al. Prevalence and determinants of rapid eye movement sleep behavior disorder in the general population. Sleep 41, zsx197 (2018).","journal-title":"Sleep"},{"key":"542_CR213","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1212\/WNL.46.2.388","volume":"46","author":"CH Schenck","year":"1996","unstructured":"Schenck, C. H., Bundlie, S. R. & Mahowald, M. W. Delayed emergence of a parkinsonian disorder in 38% of 29 older men initially diagnosed with idiopathic rapid eye movement sleep behaviour disorder. Neurology 46, 388\u2013393 (1996).","journal-title":"Neurology"},{"key":"542_CR214","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/mds.1120","volume":"16","author":"BF Boeve","year":"2001","unstructured":"Boeve, B. F., Silber, M. H., Ferman, T. J., Lucas, J. A. & Parisi, J. E. Association of REM sleep behavior disorder and neurodegenerative disease may reflect an underlying synucleinopathy. Mov. Disord. 16, 622\u2013630 (2001).","journal-title":"Mov. Disord."},{"key":"542_CR215","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1212\/01.WNL.0000073619.94467.B0","volume":"61","author":"BF Boeve","year":"2003","unstructured":"Boeve, B. F. et al. Synucleinopathy pathology and REM sleep behavior disorder plus dementia or parkinsonism. Neurology 61, 40\u201345 (2003).","journal-title":"Neurology"},{"key":"542_CR216","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1177\/0891988704267465","volume":"17","author":"BF Boeve","year":"2004","unstructured":"Boeve, B. F., Silber, M. H. & Ferman, T. J. REM sleep behavior disorder in Parkinson\u2019s disease and dementia with Lewy bodies. J. Geriatr. Psychiatry Neurol. 17, 146\u2013157 (2004).","journal-title":"J. Geriatr. Psychiatry Neurol."},{"key":"542_CR217","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1093\/brain\/awh322","volume":"128","author":"K Stiasny-Kolster","year":"2005","unstructured":"Stiasny-Kolster, K. et al. Combination of \u2018idiopathic\u2019 REM sleep behaviour disorder and olfactory dysfunction as possible indicator for alpha-synucleinopathy demonstrated by dopamine transporter FP-CIT-SPECT. Brain 128, 126\u2013137 (2005).","journal-title":"Brain"},{"key":"542_CR218","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1212\/01.wnl.0000209264.61035.bb","volume":"66","author":"BF Boeve","year":"2006","unstructured":"Boeve, B. F. & Saper, C. B. REM sleep behavior disorder: a possible early marker for synucleinopathies. Neurology 66, 796\u2013797 (2006).","journal-title":"Neurology"},{"key":"542_CR219","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1016\/S1474-4422(06)70441-0","volume":"5","author":"J-F Gagnon","year":"2006","unstructured":"Gagnon, J.-F., Postuma, R. B., Mazza, S., Doyon, J. & Montplaisir, J. Rapid-eye-movement sleep behaviour disorder and neurodegenerative diseases. Lancet Neurol. 5, 424\u2013432 (2006).","journal-title":"Lancet Neurol."},{"key":"542_CR220","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1212\/01.wnl.0000203648.80727.5b","volume":"66","author":"RB Postuma","year":"2006","unstructured":"Postuma, R. B., Lang, A. E., Massicotte-Marquez, J. & Montplaisir, J. Potential early markers of Parkinson disease in idiopathic REM sleep behavior disorder. Neurology 66, 845\u2013851 (2006).","journal-title":"Neurology"},{"key":"542_CR221","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s10072-016-2744-1","volume":"38","author":"X Zhang","year":"2017","unstructured":"Zhang, X., Sun, X., Wang, J., Tang, L. & Xie, A. Prevalence of rapid eye movement sleep behavior disorder (RBD) in Parkinson\u2019s disease: a meta and meta-regression analysis. Neurol. Sci. 38, 163\u2013170 (2017).","journal-title":"Neurol. Sci."},{"key":"542_CR222","doi-asserted-by":"publisher","DOI":"10.1186\/s12883-017-0795-4","volume":"17","author":"J Zhang","year":"2017","unstructured":"Zhang, J., Xu, C.-Y. & Liu, J. Meta-analysis on the prevalence of REM sleep behavior disorder symptoms in Parkinson\u2019s disease. BMC Neurol. 17, 23 (2017).","journal-title":"BMC Neurol."},{"key":"542_CR223","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/j.sleep.2012.10.009","volume":"14","author":"CH Schenck","year":"2013","unstructured":"Schenck, C. H., Boeve, B. F. & Mahowald, M. W. Delayed emergence of a parkinsonian disorder or dementia in 81% of older men initially diagnosed with idiopathic rapid eye movement sleep behavior disorder: a 16-year update on a previously reported series. Sleep Med. 14, 744\u2013748 (2013).","journal-title":"Sleep Med."},{"key":"542_CR224","doi-asserted-by":"publisher","first-page":"526","DOI":"10.1212\/WNL.51.2.526","volume":"51","author":"CL Comella","year":"1998","unstructured":"Comella, C. L., Nardine, T. M., Diederich, N. J. & Stebbins, G. T. Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson\u2019s disease. Neurology 51, 526\u2013529 (1998).","journal-title":"Neurology"},{"key":"542_CR225","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1212\/WNL.59.4.585","volume":"59","author":"JF Gagnon","year":"2002","unstructured":"Gagnon, J. F. et al. REM sleep behavior disorder and REM sleep without atonia in Parkinson\u2019s disease. Neurology 59, 585\u2013589 (2002).","journal-title":"Neurology"},{"issue":"Suppl. 2","key":"542_CR226","doi-asserted-by":"publisher","first-page":"S656","DOI":"10.1002\/mds.22672","volume":"24","author":"C Gaig","year":"2009","unstructured":"Gaig, C. & Tolosa, E. When does Parkinson\u2019s disease begin? Mov. Disord. 24 (Suppl. 2), S656\u2013S664 (2009).","journal-title":"Mov. Disord."},{"key":"542_CR227","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/j.parkreldis.2011.03.007","volume":"17","author":"CH Adler","year":"2011","unstructured":"Adler, C. H. et al. Probable RBD is increased in Parkinson\u2019s disease but not in essential tremor or restless legs syndrome. Parkinsonism Relat. Disord. 17, 456\u2013458 (2011).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR228","first-page":"7657191","volume":"2018","author":"P Gomutbutra","year":"2018","unstructured":"Gomutbutra, P., Kanjanaratanakorn, K. & Tiyapun, N. Prevalence and clinical characteristics of probable REM behavior disorder in Thai Parkinson\u2019s disease patients. Parkinsons. Dis. 2018, 7657191 (2018).","journal-title":"Parkinsons. Dis."},{"key":"542_CR229","doi-asserted-by":"publisher","first-page":"e1171","DOI":"10.1212\/WNL.0000000000008127","volume":"93","author":"SJ McCarter","year":"2019","unstructured":"McCarter, S. J. et al. REM sleep muscle activity in idiopathic REM sleep behavior disorder predicts phenoconversion. Neurology 93, e1171\u2013e1179 (2019).","journal-title":"Neurology"},{"key":"542_CR230","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.sleep.2019.09.013","volume":"68","author":"M Miyamoto","year":"2020","unstructured":"Miyamoto, M., Miyamoto, T., Saitou, J. & Sato, T. Longitudinal study of striatal aromatic l-amino acid decarboxylase activity in patients with idiopathic rapid eye movement sleep behavior disorder. Sleep. Med. 68, 50\u201356 (2020).","journal-title":"Sleep. Med."},{"key":"542_CR231","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1093\/brain\/awaa238","volume":"143","author":"J Horsager","year":"2020","unstructured":"Horsager, J. et al. Brain-first versus body-first Parkinson\u2019s disease: a multimodal imaging case-control study. Brain 143, 3077\u20133088 (2020). This paper discusses the existence of two subtypes of PD: brain-first, where \u03b1-syn pathology initially arises in the brain with secondary spreading to the peripheral autonomic nervous system, and body-first, where the pathology originates in the peripheral autonomic nervous system and then spreads to the brain.","journal-title":"Brain"},{"key":"542_CR232","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1212\/WNL.48.4.1094","volume":"48","author":"G Plazzi","year":"1997","unstructured":"Plazzi, G. et al. REM sleep behavior disorders in multiple system atrophy. Neurology 48, 1094\u20131097 (1997).","journal-title":"Neurology"},{"key":"542_CR233","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1136\/jnnp.63.5.678","volume":"63","author":"N Tachibana","year":"1997","unstructured":"Tachibana, N. et al. REM sleep motor dysfunction in multiple system atrophy: with special emphasis on sleep talk as its early clinical manifestation. J. Neurol. Neurosurg. Psychiatry 63, 678\u2013681 (1997).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR234","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1002\/mds.24939","volume":"27","author":"RB Postuma","year":"2012","unstructured":"Postuma, R. B. et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson\u2019s disease: a prospective study. Mov. Disord. 27, 720\u2013726 (2012).","journal-title":"Mov. Disord."},{"key":"542_CR235","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1212\/WNL.0000000000000842","volume":"83","author":"JBMM Anang","year":"2014","unstructured":"Anang, J. B. M. M. et al. Predictors of dementia in Parkinson disease: a prospective cohort study. Neurology 83, 1253\u20131260 (2014).","journal-title":"Neurology"},{"key":"542_CR236","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.parkreldis.2009.08.005","volume":"16","author":"JE Lee","year":"2010","unstructured":"Lee, J. E., Kim, K. S., Shin, H. W. & Sohn, Y. H. Factors related to clinically probable REM sleep behavior disorder in Parkinson disease. Parkinsonism Relat. Disord. 16, 105\u2013108 (2010).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR237","doi-asserted-by":"publisher","first-page":"1048","DOI":"10.1212\/WNL.0b013e31822e560e","volume":"77","author":"F Sixel-D\u00f6ring","year":"2011","unstructured":"Sixel-D\u00f6ring, F., Trautmann, E., Mollenhauer, B. & Trenkwalder, C. Associated factors for REM sleep behavior disorder in Parkinson disease. Neurology 77, 1048\u20131054 (2011).","journal-title":"Neurology"},{"key":"542_CR238","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1136\/jnnp.2007.116830","volume":"79","author":"MD Gjerstad","year":"2008","unstructured":"Gjerstad, M. D., Boeve, B., Wentzel-Larsen, T., Aarsland, D. & Larsen, J. P. Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson\u2019s disease over time. J. Neurol. Neurosurg. Psychiatry 79, 387\u2013391 (2008).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR239","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/j.parkreldis.2013.07.017","volume":"19","author":"P Bugalho","year":"2013","unstructured":"Bugalho, P. & Viana-Baptista, M. REM sleep behavior disorder and motor dysfunction in Parkinson\u2019s disease \u2014 a longitudinal study. Parkinsonism Relat. Disord. 19, 1084\u20131087 (2013).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR240","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1111\/ene.12723","volume":"22","author":"KA Bj\u00f8rnar\u00e5","year":"2015","unstructured":"Bj\u00f8rnar\u00e5, K. A., Dietrichs, E. & Toft, M. Longitudinal assessment of probable rapid eye movement sleep behaviour disorder in Parkinson\u2019s disease. Eur. J. Neurol. 22, 1242\u20131244 (2015).","journal-title":"Eur. J. Neurol."},{"key":"542_CR241","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.sleep.2019.12.013","volume":"68","author":"M Figorilli","year":"2020","unstructured":"Figorilli, M. et al. Does REM sleep behavior disorder change in the progression of Parkinson\u2019s disease? Sleep. Med. 68, 190\u2013198 (2020).","journal-title":"Sleep. Med."},{"key":"542_CR242","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1007\/s00415-010-5679-0","volume":"258","author":"P Bugalho","year":"2011","unstructured":"Bugalho, P., da Silva, J. A. & Neto, B. Clinical features associated with REM sleep behavior disorder symptoms in the early stages of Parkinson\u2019s disease. J. Neurol. 258, 50\u201355 (2011).","journal-title":"J. Neurol."},{"key":"542_CR243","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1007\/s11325-013-0887-3","volume":"18","author":"R Ferri","year":"2014","unstructured":"Ferri, R. et al. The timing between REM sleep behavior disorder and Parkinson\u2019s disease. Sleep. Breath. 18, 319\u2013323 (2014).","journal-title":"Sleep. Breath."},{"key":"542_CR244","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1016\/j.jns.2017.08.3247","volume":"382","author":"T Nomura","year":"2017","unstructured":"Nomura, T., Kishi, M. & Nakashima, K. Differences in clinical characteristics when REM sleep behavior disorder precedes or comes after the onset of Parkinson\u2019s disease. J. Neurol. Sci. 382, 58\u201360 (2017).","journal-title":"J. Neurol. Sci."},{"key":"542_CR245","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1212\/WNL.55.9.1410","volume":"55","author":"RL Albin","year":"2000","unstructured":"Albin, R. L. et al. Decreased striatal dopaminergic innervation in REM sleep behavior disorder. Neurology 55, 1410\u20131412 (2000).","journal-title":"Neurology"},{"key":"542_CR246","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1093\/brain\/123.6.1155","volume":"123","author":"I Eisensehr","year":"2000","unstructured":"Eisensehr, I. et al. Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson\u2019s disease and controls. Brain 123, 1155\u20131160 (2000).","journal-title":"Brain"},{"key":"542_CR247","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1093\/sleep\/26.5.507","volume":"26","author":"I Eisensehr","year":"2003","unstructured":"Eisensehr, I. et al. Increased muscle activity during rapid eye movement sleep correlates with decrease of striatal presynaptic dopamine transporters. IPT and IBZM SPECT imaging in subclinical and clinically manifest idiopathic REM sleep behavior disorder, Parkinson\u2019s disease. Sleep 26, 507\u2013512 (2003).","journal-title":"Sleep"},{"key":"542_CR248","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1002\/ana.25026","volume":"82","author":"A Iranzo","year":"2017","unstructured":"Iranzo, A. et al. Dopamine transporter imaging deficit predicts early transition to synucleinopathy in idiopathic rapid eye movement sleep behavior disorder. Ann. Neurol. 82, 419\u2013428 (2017).","journal-title":"Ann. Neurol."},{"key":"542_CR249","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1002\/ana.25103","volume":"82","author":"V Kaasinen","year":"2017","unstructured":"Kaasinen, V. & Vahlberg, T. Striatal dopamine in Parkinson disease: a meta-analysis of imaging studies. Ann. Neurol. 82, 873\u2013882 (2017).","journal-title":"Ann. Neurol."},{"key":"542_CR250","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1212\/01.WNL.0000073745.68744.94","volume":"61","author":"S Gilman","year":"2003","unstructured":"Gilman, S. et al. REM sleep behavior disorder is related to striatal monoaminergic deficit in MSA. Neurology 61, 29\u201334 (2003).","journal-title":"Neurology"},{"key":"542_CR251","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1002\/ana.22245","volume":"69","author":"C Scherfler","year":"2011","unstructured":"Scherfler, C. et al. White and gray matter abnormalities in idiopathic rapid eye movement sleep behavior disorder: a diffusion-tensor imaging and voxel-based morphometry study. Ann. Neurol. 69, 400\u2013407 (2011).","journal-title":"Ann. Neurol."},{"key":"542_CR252","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/S1474-4422(10)70216-7","volume":"9","author":"A Iranzo","year":"2010","unstructured":"Iranzo, A. et al. Decreased striatal dopamine transporter uptake and substantia nigra hyperechogenicity as risk markers of synucleinopathy in patients with idiopathic rapid-eye-movement sleep behaviour disorder: a prospective study. Lancet Neurol. 9, 1070\u20131077 (2010).","journal-title":"Lancet Neurol."},{"key":"542_CR253","doi-asserted-by":"publisher","first-page":"2770","DOI":"10.1093\/brain\/awm056","volume":"130","author":"BF Boeve","year":"2007","unstructured":"Boeve, B. F. et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130, 2770\u20132788 (2007).","journal-title":"Brain"},{"key":"542_CR254","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.smrv.2010.08.002","volume":"15","author":"P-H Luppi","year":"2011","unstructured":"Luppi, P.-H. et al. The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) behavior disorder. Sleep. Med. Rev. 15, 153\u2013163 (2011).","journal-title":"Sleep. Med. Rev."},{"key":"542_CR255","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1002\/ana.22691","volume":"71","author":"V Kotagal","year":"2012","unstructured":"Kotagal, V. et al. Symptoms of rapid eye movement sleep behavior disorder are associated with cholinergic denervation in Parkinson disease. Ann. Neurol. 71, 560\u2013568 (2012).","journal-title":"Ann. Neurol."},{"key":"542_CR256","doi-asserted-by":"publisher","first-page":"636","DOI":"10.1002\/mds.27003","volume":"32","author":"D McKenna","year":"2017","unstructured":"McKenna, D. & Peever, J. Degeneration of rapid eye movement sleep circuitry underlies rapid eye movement sleep behavior disorder. Mov. Disord. 32, 636\u2013644 (2017).","journal-title":"Mov. Disord."},{"key":"542_CR257","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1212\/WNL.55.6.894","volume":"55","author":"K Kimura","year":"2000","unstructured":"Kimura, K. et al. A discrete pontine ischemic lesion could cause REM sleep behavior disorder. Neurology 55, 894\u2013895 (2000).","journal-title":"Neurology"},{"key":"542_CR258","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/S1389-9457(02)00042-4","volume":"3","author":"G Plazzi","year":"2002","unstructured":"Plazzi, G. & Montagna, P. Remitting REM sleep behavior disorder as the initial sign of multiple sclerosis. Sleep Med. 3, 437\u2013439 (2002).","journal-title":"Sleep Med."},{"key":"542_CR259","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1136\/jnnp.72.6.821","volume":"72","author":"T Zambelis","year":"2002","unstructured":"Zambelis, T., Paparrigopoulos, T. & Soldatos, C. R. REM sleep behaviour disorder associated with a neurinoma of the left pontocerebellar angle. J. Neurol. Neurosurge. Psychiatry 72, 821\u2013822 (2002).","journal-title":"J. Neurol. Neurosurge. Psychiatry"},{"key":"542_CR260","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.sleep.2003.07.002","volume":"5","author":"R Vetrugno","year":"2004","unstructured":"Vetrugno, R. et al. Sleep disorders in multiple system atrophy: a correlative video-polysomnographic study. Sleep Med. 5, 21\u201330 (2004).","journal-title":"Sleep Med."},{"key":"542_CR261","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1212\/01.wnl.0000208518.72660.ff","volume":"66","author":"M Tippmann-Peikert","year":"2006","unstructured":"Tippmann-Peikert, M., Boeve, B. F. & Keegan, B. M. REM sleep behavior disorder initiated by acute brainstem multiple sclerosis. Neurology 66, 1277\u20131279 (2006).","journal-title":"Neurology"},{"key":"542_CR262","doi-asserted-by":"publisher","first-page":"1059","DOI":"10.1016\/j.sleep.2008.12.006","volume":"10","author":"N Limousin","year":"2009","unstructured":"Limousin, N. et al. A brainstem inflammatory lesion causing REM sleep behavior disorder and sleepwalking (parasomnia overlap disorder). Sleep. Med. 10, 1059\u20131062 (2009).","journal-title":"Sleep. Med."},{"key":"542_CR263","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-02761-0","volume":"9","author":"S Valencia Garcia","year":"2018","unstructured":"Valencia Garcia, S. et al. Ventromedial medulla inhibitory neuron inactivation induces REM sleep without atonia and REM sleep behavior disorder. Nat. Commun. 9, 504 (2018).","journal-title":"Nat. Commun."},{"key":"542_CR264","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1016\/S1474-4422(18)30318-1","volume":"17","author":"MK Rasmussen","year":"2018","unstructured":"Rasmussen, M. K., Mestre, H. & Nedergaard, M. The glymphatic pathway in neurological disorders. Lancet Neurol. 17, 1016\u20131024 (2018).","journal-title":"Lancet Neurol."},{"key":"542_CR265","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1002\/mds.28473","volume":"36","author":"EK Donahue","year":"2021","unstructured":"Donahue, E. K. et al. Global and regional changes in perivascular space in idiopathic and familial Parkinson\u2019s disease. Mov. Disord. 36, 1126\u20131136 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR266","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1038\/s41591-020-01198-1","volume":"27","author":"X-B Ding","year":"2021","unstructured":"Ding, X.-B. et al. Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson\u2019s disease. Nat. Med. 27, 411\u2013418 (2021).","journal-title":"Nat. Med."},{"key":"542_CR267","doi-asserted-by":"publisher","first-page":"e460","DOI":"10.1212\/WNL.0000000000011155","volume":"96","author":"N Pyatigorskaya","year":"2021","unstructured":"Pyatigorskaya, N. et al. Parkinson disease propagation using MRI biomarkers and partial least squares path modeling. Neurology 96, e460\u2013e471 (2021).","journal-title":"Neurology"},{"key":"542_CR268","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1111\/j.1572-0241.2004.04114.x","volume":"99","author":"PDR Higgins","year":"2004","unstructured":"Higgins, P. D. R. & Johanson, J. F. Epidemiology of constipation in North America: a systematic review. Am. J. Gastroenterol. 99, 750\u2013759 (2004).","journal-title":"Am. J. Gastroenterol."},{"key":"542_CR269","doi-asserted-by":"publisher","first-page":"1371","DOI":"10.1016\/j.parkreldis.2014.09.026","volume":"20","author":"C-H Lin","year":"2014","unstructured":"Lin, C.-H., Lin, J.-W., Liu, Y.-C., Chang, C.-H. & Wu, R.-M. Risk of Parkinson\u2019s disease following severe constipation: a nationwide population-based cohort study. Parkinsonism Relat. Disord. 20, 1371\u20131375 (2014).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR270","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1007\/s10072-018-3502-3","volume":"39","author":"X Guan","year":"2018","unstructured":"Guan, X. et al. Analysis of the clinical features of early Parkinson\u2019s disease with comparatively integrated intestinal function. Neurol. Sci. 39, 1847\u20131856 (2018).","journal-title":"Neurol. Sci."},{"key":"542_CR271","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1001\/jamaneurol.2018.4377","volume":"76","author":"E De Pablo-Fern\u00e1ndez","year":"2019","unstructured":"De Pablo-Fern\u00e1ndez, E., Lees, A. J., Holton, J. L. & Warner, T. T. Prognosis and neuropathologic correlation of clinical subtypes of Parkinson disease. JAMA Neurol. 76, 470\u2013479 (2019).","journal-title":"JAMA Neurol."},{"key":"542_CR272","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1016\/bs.irn.2017.06.003","volume":"134","author":"F Stocchi","year":"2017","unstructured":"Stocchi, F. & Torti, M. Constipation in Parkinson\u2019s disease. Int. Rev. Neurobiol. 134, 811\u2013826 (2017).","journal-title":"Int. Rev. Neurobiol."},{"key":"542_CR273","doi-asserted-by":"publisher","first-page":"621","DOI":"10.3389\/fneur.2019.00621","volume":"10","author":"G Frazzitta","year":"2019","unstructured":"Frazzitta, G., Ferrazzoli, D., Folini, A., Palamara, G. & Maestri, R. Severe Constipation in Parkinson\u2019s disease and in parkinsonisms: prevalence and affecting factors. Front. Neurol. 10, 621 (2019).","journal-title":"Front. Neurol."},{"key":"542_CR274","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.parkreldis.2019.07.008","volume":"66","author":"I Stankovic","year":"2019","unstructured":"Stankovic, I. et al. Longitudinal assessment of autonomic dysfunction in early Parkinson\u2019s disease. Parkinsonism Relat. Disord. 66, 74\u201379 (2019).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR275","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.jns.2009.07.026","volume":"287","author":"HJ Kim","year":"2009","unstructured":"Kim, H. J. et al. Nonmotor symptoms in de novo Parkinson disease before and after dopaminergic treatment. J. Neurol. Sci. 287, 200\u2013204 (2009).","journal-title":"J. Neurol. Sci."},{"key":"542_CR276","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1002\/mds.23387","volume":"26","author":"B M\u00fcller","year":"2011","unstructured":"M\u00fcller, B., Larsen, J. P., Wentzel-Larsen, T., Skeie, G. O. & Tysnes, O. B. Autonomic and sensory symptoms and signs in incident, untreated Parkinson\u2019s disease: frequent but mild. Mov. Disord. 26, 65\u201372 (2011).","journal-title":"Mov. Disord."},{"key":"542_CR277","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1002\/mds.26077","volume":"30","author":"C Pont-Sunyer","year":"2015","unstructured":"Pont-Sunyer, C. et al. The onset of nonmotor symptoms in Parkinson\u2019s disease (the ONSET PD study). Mov. Disord. 30, 229\u2013237 (2015).","journal-title":"Mov. Disord."},{"key":"542_CR278","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41575-020-0271-2","volume":"17","author":"NJ Spencer","year":"2020","unstructured":"Spencer, N. J. & Hu, H. Enteric nervous system: sensory transduction, neural circuits and gastrointestinal motility. Nat. Rev. Gastroenterol. Hepatol. 17, 338\u2013351 (2020).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"542_CR279","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nrn3071","volume":"12","author":"EA Mayer","year":"2011","unstructured":"Mayer, E. A. Gut feelings: the emerging biology of gut-brain communication. Nat. Rev. Neurosci. 12, 453\u2013466 (2011). This paper reviews the connection between the gut and the brain, showing that this interaction plays an important role not only in gastrointestinal function but also in certain brain functions.","journal-title":"Nat. Rev. Neurosci."},{"key":"542_CR280","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1016\/j.neuron.2019.02.008","volume":"101","author":"C F\u00fclling","year":"2019","unstructured":"F\u00fclling, C., Dinan, T. G. & Cryan, J. F. Gut microbe to brain signaling: what happens in Vagus\u2026. Neuron 101, 998\u20131002 (2019).","journal-title":"Neuron"},{"key":"542_CR281","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1038\/s41586-020-2474-7","volume":"583","author":"PA Muller","year":"2020","unstructured":"Muller, P. A. et al. Microbiota modulate sympathetic neurons via a gut\u2013brain circuit. Nature 583, 441\u2013446 (2020).","journal-title":"Nature"},{"key":"542_CR282","first-page":"621","volume":"101","author":"RW Countee","year":"1977","unstructured":"Countee, R. W. Extrinsic neural influences on gastrointestinal motility. Am. Surg. 101, 621\u2013626 (1977).","journal-title":"Am. Surg."},{"key":"542_CR283","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1002\/cphy.c130055","volume":"4","author":"KN Browning","year":"2014","unstructured":"Browning, K. N. & Travagli, R. A. Central nervous system control of gastrointestinal motility and secretion and modulation of gastrointestinal functions. Compr. Physiol. 4, 1339\u20131368 (2014).","journal-title":"Compr. Physiol."},{"key":"542_CR284","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/s41586-020-2425-3","volume":"585","author":"T Teratani","year":"2020","unstructured":"Teratani, T. et al. The liver\u2013brain\u2013gut neural arc maintains the Treg cell niche in the gut. Nature 585, 591\u2013596 (2020).","journal-title":"Nature"},{"key":"542_CR285","doi-asserted-by":"publisher","first-page":"13078","DOI":"10.1073\/pnas.2002737117","volume":"117","author":"DJ Levinthal","year":"2020","unstructured":"Levinthal, D. J. & Strick, P. L. Multiple areas of the cerebral cortex influence the stomach. Proc. Natl Acad. Sci. USA 117, 13078\u201313083 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"542_CR286","doi-asserted-by":"publisher","first-page":"e33321","DOI":"10.7554\/eLife.33321","volume":"7","author":"I Rebollo","year":"2018","unstructured":"Rebollo, I., Devauchelle, A.-D., B\u00e9ranger, B. & Tallon-Baudry, C. Stomach-brain synchrony reveals a novel, delayed-connectivity resting-state network in humans. eLife 7, e33321 (2018).","journal-title":"eLife"},{"key":"542_CR287","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1136\/gutjnl-2011-300474","volume":"61","author":"NA Koloski","year":"2012","unstructured":"Koloski, N. A. et al. The brain\u2013gut pathway in functional gastrointestinal disorders is bidirectional: a 12-year prospective population-based study. Gut 61, 1284\u20131290 (2012).","journal-title":"Gut"},{"key":"542_CR288","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/nrgastro.2016.191","volume":"14","author":"N Powell","year":"2017","unstructured":"Powell, N., Walker, M. M. & Talley, N. J. The mucosal immune system: Master regulator of bidirectional gut-brain communications. Nat. Rev. Gastroenterol. Hepatol. 14, 143\u2013159 (2017).","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"542_CR289","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.expneurol.2007.05.010","volume":"207","author":"G Anderson","year":"2007","unstructured":"Anderson, G. et al. Loss of enteric dopaminergic neurons and associated changes in colon motility in an MPTP mouse model of Parkinson\u2019s disease. Exp. Neurol. 207, 4\u201312 (2007).","journal-title":"Exp. Neurol."},{"key":"542_CR290","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.neuropharm.2017.05.016","volume":"123","author":"C Pellegrini","year":"2017","unstructured":"Pellegrini, C. et al. Effects of L-DOPA\/benserazide co-treatment on colonic excitatory cholinergic motility and enteric inflammation following dopaminergic nigrostriatal neurodegeneration. Neuropharmacology 123, 22\u201333 (2017).","journal-title":"Neuropharmacology"},{"key":"542_CR291","doi-asserted-by":"publisher","first-page":"e13726","DOI":"10.1111\/nmo.13726","volume":"32","author":"SM O\u2019Donovan","year":"2020","unstructured":"O\u2019Donovan, S. M. et al. Nigral overexpression of \u03b1-synuclein in a rat Parkinson\u2019s disease model indicates alterations in the enteric nervous system and the gut microbiome. Neurogastroenterol. Motil. 32, e13726 (2020).","journal-title":"Neurogastroenterol. Motil."},{"key":"542_CR292","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1002\/mds.26069","volume":"30","author":"F Scheperjans","year":"2015","unstructured":"Scheperjans, F. et al. Gut microbiota are related to Parkinson\u2019s disease and clinical phenotype. Mov. Disord. 30, 350\u2013358 (2015).","journal-title":"Mov. Disord."},{"key":"542_CR293","doi-asserted-by":"publisher","first-page":"e00028","DOI":"10.1128\/MMBR.00028-18","volume":"82","author":"SA Tursi","year":"2018","unstructured":"Tursi, S. A. & T\u00fckel, \u00c7. Curli-containing enteric biofilms inside and out: matrix composition, immune recognition, and disease implications. Microbiol. Mol. Biol. Rev. 82, e00028\u201318 (2018).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"542_CR294","doi-asserted-by":"publisher","first-page":"1351","DOI":"10.1002\/mds.26307","volume":"30","author":"A Keshavarzian","year":"2015","unstructured":"Keshavarzian, A. et al. Colonic bacterial composition in Parkinson\u2019s disease. Mov. Disord. 30, 1351\u20131360 (2015).","journal-title":"Mov. Disord."},{"key":"542_CR295","doi-asserted-by":"publisher","first-page":"e0142164","DOI":"10.1371\/journal.pone.0142164","volume":"10","author":"S Hasegawa","year":"2015","unstructured":"Hasegawa, S. et al. Intestinal dysbiosis and lowered serum lipopolysaccharide-binding protein in Parkinson\u2019s disease. PLoS One 10, e0142164 (2015).","journal-title":"PLoS One"},{"key":"542_CR296","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.parkreldis.2016.08.019","volume":"32","author":"MM Unger","year":"2016","unstructured":"Unger, M. M. et al. Short chain fatty acids and gut microbiota differ between patients with Parkinson\u2019s disease and age-matched controls. Parkinsonism Relat. Disord. 32, 66\u201372 (2016).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR297","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1136\/pgmj.72.845.164","volume":"72","author":"KN Davies","year":"1996","unstructured":"Davies, K. N., King, D., Billington, D. & Barrett, J. A. Intestinal permeability and orocaecal transit time in elderly patients with Parkinson\u2019s disease. Postgrad. Med. J. 72, 164\u2013167 (1996).","journal-title":"Postgrad. Med. J."},{"key":"542_CR298","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1017\/S0317167100013202","volume":"39","author":"D Salat-Foix","year":"2012","unstructured":"Salat-Foix, D., Tran, K., Ranawaya, R., Meddings, J. & Suchowersky, O. Increased intestinal permeability and Parkinson disease patients: chicken or egg? Can. J. Neurol. Sci. 39, 185\u2013188 (2012).","journal-title":"Can. J. Neurol. Sci."},{"key":"542_CR299","doi-asserted-by":"publisher","first-page":"e28032","DOI":"10.1371\/journal.pone.0028032","volume":"6","author":"CB Forsyth","year":"2011","unstructured":"Forsyth, C. B. et al. Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson\u2019s disease. PLoS One 6, e28032 (2011).","journal-title":"PLoS One"},{"key":"542_CR300","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1002\/mds.26942","volume":"32","author":"EM Hill-Burns","year":"2017","unstructured":"Hill-Burns, E. M. et al. Parkinson\u2019s disease and Parkinson\u2019s disease medications have distinct signatures of the gut microbiome. Mov. Disord. 32, 739\u2013749 (2017).","journal-title":"Mov. Disord."},{"key":"542_CR301","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s40478-015-0196-0","volume":"3","author":"T Clairembault","year":"2015","unstructured":"Clairembault, T. et al. Structural alterations of the intestinal epithelial barrier in Parkinson\u2019s disease. Acta Neuropathol. Commun. 3, 12 (2015).","journal-title":"Acta Neuropathol. Commun."},{"key":"542_CR302","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1002\/mds.28594","volume":"36","author":"X Kang","year":"2021","unstructured":"Kang, X., Ploner, A., Roelstraete, B., Khalili, H. & Wirdefeldt, K. Association between microscopic colitis and Parkinson\u2019 s disease in a Swedish population. Mov. Disord. 36, 1919\u20131926 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR303","doi-asserted-by":"publisher","first-page":"785","DOI":"10.1002\/mds.28526","volume":"36","author":"P Borghammer","year":"2021","unstructured":"Borghammer, P. & Horsager, J. The logic and pitfalls of Parkinson\u2019s as brain- versus body-first subtypes. Mov. Disord. 36, 785\u2013786 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR304","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1007\/s00401-016-1661-y","volume":"133","author":"A Ulusoy","year":"2017","unstructured":"Ulusoy, A. et al. Brain-to-stomach transfer of alpha-synuclein via vagal preganglionic projections. Acta Neuropathol. 133, 381\u2013393 (2017).","journal-title":"Acta Neuropathol."},{"key":"542_CR305","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1093\/brain\/awaa096","volume":"143","author":"ML Arotcarena","year":"2020","unstructured":"Arotcarena, M. L. et al. Bidirectional gut-to-brain and brain-to-gut propagation of synucleinopathy in non-human primates. Brain 143, 1462\u20131475 (2020). This study showed that progression of \u03b1-syn pathology in a non-human primate model of PD might be either bottom-up or top-down in the absence of pathology through the vagus nerve and the dorsal motor nucleus of the vagus.","journal-title":"Brain"},{"key":"542_CR306","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1007\/s00401-019-02040-w","volume":"138","author":"N Van Den Berge","year":"2019","unstructured":"Van Den Berge, N. et al. Evidence for bidirectional and trans-synaptic parasympathetic and sympathetic propagation of alpha-synuclein in rats. Acta Neuropathol. 138, 535\u2013550 (2019).","journal-title":"Acta Neuropathol."},{"key":"542_CR307","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/s41582-021-00486-9","volume":"17","author":"D Berg","year":"2021","unstructured":"Berg, D. et al. Prodromal Parkinson disease subtypes \u2014 key to understanding heterogeneity. Nat. Rev. Neurol. 17, 349\u2013361 (2021).","journal-title":"Nat. Rev. Neurol."},{"key":"542_CR308","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.tins.2016.10.008","volume":"40","author":"S Engelender","year":"2017","unstructured":"Engelender, S. & Isacson, O. The threshold theory for Parkinson\u2019s disease. Trends Neurosci. 40, 4\u201314 (2017).","journal-title":"Trends Neurosci."},{"key":"542_CR309","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1186\/s40478-019-0787-2","volume":"7","author":"ZA Sorrentino","year":"2019","unstructured":"Sorrentino, Z. A. et al. Unique \u03b1-synuclein pathology within the amygdala in Lewy body dementia: implications for disease initiation and progression. Acta Neuropathol. Commun. 7, 142 (2019).","journal-title":"Acta Neuropathol. Commun."},{"key":"542_CR310","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1016\/S0306-4522(00)00092-0","volume":"97","author":"JL Fudge","year":"2000","unstructured":"Fudge, J. L. & Haber, S. N. The central nucleus of the amygdala projection to dopamine subpopulations in primates. Neuroscience 97, 479\u2013494 (2000).","journal-title":"Neuroscience"},{"key":"542_CR311","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1101\/gr.160301","volume":"11","author":"RM Younger","year":"2001","unstructured":"Younger, R. M. et al. Characterization of clustered MHC-linked olfactory receptor genes in human and mouse. Genome Res. 11, 519\u2013530 (2001).","journal-title":"Genome Res."},{"key":"542_CR312","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1016\/S0896-6273(02)00793-6","volume":"35","author":"A Vassalli","year":"2002","unstructured":"Vassalli, A., Rothman, A., Feinstein, P., Zapotocky, M. & Mombaerts, P. Minigenes impart odorant receptor-specific axon guidance in the olfactory bulb. Neuron 35, 681\u2013696 (2002).","journal-title":"Neuron"},{"key":"542_CR313","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.cell.2004.05.013","volume":"117","author":"P Feinstein","year":"2004","unstructured":"Feinstein, P., Bozza, T., Rodriguez, I., Vassalli, A. & Mombaerts, P. Axon guidance of mouse olfactory sensory neurons by odorant receptors and the \u03b22 adrenergic receptor. Cell 117, 833\u2013846 (2004).","journal-title":"Cell"},{"key":"542_CR314","doi-asserted-by":"publisher","first-page":"163","DOI":"10.3389\/fnagi.2016.00163","volume":"8","author":"I Ferrer","year":"2016","unstructured":"Ferrer, I. et al. Olfactory receptors in non-chemosensory organs: the nervous system in health and disease. Front. Aging Neurosci. 8, 163 (2016).","journal-title":"Front. Aging Neurosci."},{"key":"542_CR315","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-729","volume":"15","author":"A Grison","year":"2014","unstructured":"Grison, A. et al. Mesencephalic dopaminergic neurons express a repertoire of olfactory receptors and respond to odorant-like molecules. BMC Genomics 15, 729 (2014).","journal-title":"BMC Genomics"},{"key":"542_CR316","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1097\/NEN.0b013e318294fd76","volume":"72","author":"P Garcia-Esparcia","year":"2013","unstructured":"Garcia-Esparcia, P. et al. Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain. J. Neuropathol. Exp. Neurol. 72, 524\u2013539 (2013).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"542_CR317","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1038\/s41582-020-0344-4","volume":"16","author":"EK Tan","year":"2020","unstructured":"Tan, E. K. et al. Parkinson disease and the immune system \u2014 associations, mechanisms and therapeutics. Nat. Rev. Neurol. 16, 303\u2013318 (2020).","journal-title":"Nat. Rev. Neurol."},{"key":"542_CR318","doi-asserted-by":"publisher","first-page":"3717","DOI":"10.1093\/brain\/awaa269","volume":"143","author":"J Galiano-Landeira","year":"2020","unstructured":"Galiano-Landeira, J., Torra,, A., Vila, M. & Bov\u00e9, J. CD8 T cell nigral infiltration precedes synucleinopathy in early stages of Parkinson\u2019s disease. Brain 143, 3717\u20133733 (2020).","journal-title":"Brain"},{"key":"542_CR319","doi-asserted-by":"publisher","first-page":"650","DOI":"10.1038\/s41586-021-04059-0","volume":"599","author":"P Gonz\u00e1lez-Rodr\u00edgue","year":"2021","unstructured":"Gonz\u00e1lez-Rodr\u00edguez, P. et al. Disruption of mitochondrial complex I induces progressive parkinsonism. Nature 599, 650\u2013656 (2021).","journal-title":"Nature"},{"key":"542_CR320","doi-asserted-by":"publisher","first-page":"1440","DOI":"10.1002\/mds.27776","volume":"34","author":"M Vila","year":"2019","unstructured":"Vila, M. Neuromelanin, aging, and neuronal vulnerability in Parkinson\u2019s disease. Mov. Disord. 34, 1440\u20131451 (2019).","journal-title":"Mov. Disord."},{"key":"542_CR321","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1002\/mds.28411","volume":"36","author":"EM Kline","year":"2021","unstructured":"Kline, E. M. et al. Genetic and environmental factors in Parkinson\u2019s disease converge on immune function and inflammation. Mov. Disord. 36, 25\u201336 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR322","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1111\/j.1440-1789.2007.00803.x","volume":"27","author":"K Wakabayashi","year":"2007","unstructured":"Wakabayashi, K., Tanji, K., Mori, F. & Takahashi, H. The Lewy body in Parkinson\u2019s disease: molecules implicated in the formation and degradation of \u03b1-synuclein aggregates. Neuropathology 27, 494\u2013506 (2007).","journal-title":"Neuropathology"},{"key":"542_CR323","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.jneumeth.2016.03.016","volume":"266","author":"A McCormack","year":"2016","unstructured":"McCormack, A. et al. Purification of \u03b1-synuclein containing inclusions from human post mortem brain tissue. J. Neurosci. Methods 266, 141\u2013150 (2016).","journal-title":"J. Neurosci. Methods"},{"key":"542_CR324","doi-asserted-by":"publisher","first-page":"3850","DOI":"10.2741\/2973","volume":"13","author":"Q Xia","year":"2008","unstructured":"Xia, Q. et al. Proteomic identification of novel proteins associated with Lewy bodies. Front. Biosci. 13, 3850\u20133856 (2008).","journal-title":"Front. Biosci."},{"key":"542_CR325","doi-asserted-by":"publisher","first-page":"eaaz9165","DOI":"10.1126\/sciadv.aaz9165","volume":"6","author":"M Bourdenx","year":"2020","unstructured":"Bourdenx, M. et al. Identification of distinct pathological signatures induced by patient-derived \u03b1-synuclein structures in nonhuman primates. Sci. Adv. 6, eaaz9165 (2020).","journal-title":"Sci. Adv."},{"key":"542_CR326","doi-asserted-by":"publisher","first-page":"e21791","DOI":"10.1096\/fj.202100201RR","volume":"35","author":"C Ducrot","year":"2021","unstructured":"Ducrot, C. et al. Dopaminergic neurons establish a distinctive axonal arbor with a majority of non-synaptic terminals. FASEB J. 35, e21791 (2021).","journal-title":"FASEB J."},{"key":"542_CR327","doi-asserted-by":"publisher","first-page":"152","DOI":"10.3389\/fnana.2014.00152","volume":"8","author":"L Brichta","year":"2014","unstructured":"Brichta, L. & Greengard, P. Molecular determinants of selective dopaminergic vulnerability in Parkinson\u2019s disease: an update. Front. Neuroanat. 8, 152 (2014).","journal-title":"Front. Neuroanat."},{"key":"542_CR328","doi-asserted-by":"publisher","first-page":"2558","DOI":"10.1093\/brain\/awz193","volume":"142","author":"MJ Betts","year":"2019","unstructured":"Betts, M. J. et al. Locus coeruleus imaging as a biomarker for noradrenergic dysfunction in neurodegenerative diseases. Brain 142, 2558\u20132571 (2019).","journal-title":"Brain"},{"key":"542_CR329","doi-asserted-by":"publisher","first-page":"455","DOI":"10.3389\/fneur.2018.00455","volume":"9","author":"N Gigu\u00e8re","year":"2018","unstructured":"Gigu\u00e8re, N., Burke Nanni, S. & Trudeau, L.-E. On cell loss and selective vulnerability of neuronal populations in Parkinson\u2019s disease. Front. Neurol. 9, 455 (2018).","journal-title":"Front. Neurol."},{"key":"542_CR330","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1002\/mds.27785","volume":"34","author":"WH Oertel","year":"2019","unstructured":"Oertel, W. H., Henrich, M. T., Janzen, A. & Geibl, F. F. The locus coeruleus: another vulnerability target in Parkinson\u2019s disease. Mov. Disord. 34, 1423\u20131429 (2019).","journal-title":"Mov. Disord."},{"key":"542_CR331","doi-asserted-by":"publisher","first-page":"435","DOI":"10.3389\/fphar.2020.00435","volume":"11","author":"E Paredes-Rodriguez","year":"2020","unstructured":"Paredes-Rodriguez, E., Vegas-Suarez, S., Morera-Herreras, T., De Deurwaerdere, P. & Miguelez, C. The noradrenergic system in Parkinson\u2019s disease. Front. Pharmacol. 11, 435 (2020).","journal-title":"Front. Pharmacol."},{"key":"542_CR332","doi-asserted-by":"publisher","first-page":"2243","DOI":"10.1093\/brain\/awab111","volume":"144","author":"N Holland","year":"2021","unstructured":"Holland, N., Robbins, T. W. & Rowe, J. B. The role of noradrenaline in cognition and cognitive disorders. Brain 144, 2243\u20132256 (2021).","journal-title":"Brain"},{"key":"542_CR333","doi-asserted-by":"publisher","first-page":"e1007","DOI":"10.1212\/WNL.0000000000012444","volume":"97","author":"J Prasuhn","year":"2021","unstructured":"Prasuhn, J. et al. Association of locus coeruleus and substantia nigra pathology with cognitive and motor functions in patients with Parkinson disease. Neurology 97, e1007\u2013e1016 (2021).","journal-title":"Neurology"},{"key":"542_CR334","doi-asserted-by":"publisher","first-page":"789","DOI":"10.1148\/radiol.2016160662","volume":"283","author":"ST Schwarz","year":"2017","unstructured":"Schwarz, S. T., Xing, Y., Tomar, P., Bajaj, N. & Auer, D. P. In vivo assessment of brainstem depigmentation in Parkinson disease: potential as a severity marker for multicenter studies. Radiology 283, 789\u2013798 (2017).","journal-title":"Radiology"},{"key":"542_CR335","doi-asserted-by":"publisher","first-page":"2732","DOI":"10.1093\/brain\/awab236","volume":"144","author":"CEJ Doppler","year":"2021","unstructured":"Doppler, C. E. J. et al. Regional locus coeruleus degeneration is uncoupled from noradrenergic terminal loss in Parkinson\u2019s disease. Brain 144, 2732\u20132744 (2021).","journal-title":"Brain"},{"key":"542_CR336","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1007\/s00702-002-0808-2","volume":"110","author":"H Braak","year":"2003","unstructured":"Braak, H., R\u00fcb, U., Gai, W. P. & Del Tredici, K. Idiopathic Parkinson\u2019s disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen. J. Neural Transm. 110, 517\u2013536 (2003).","journal-title":"J. Neural Transm."},{"key":"542_CR337","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/ana.410270405","volume":"27","author":"GM Halliday","year":"1990","unstructured":"Halliday, G. M. et al. Neuropathology of immunohistochemically identified brainstem neurons in Parkinson\u2019s disease. Ann. Neurol. 27, 373\u2013385 (1990).","journal-title":"Ann. Neurol."},{"key":"542_CR338","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1038\/334345a0","volume":"334","author":"E Hirsch","year":"1988","unstructured":"Hirsch, E., Graybiel, A. M. & Agid, Y. A. Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson\u2019s disease. Nature 334, 345\u2013348 (1988).","journal-title":"Nature"},{"key":"542_CR339","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1016\/j.bbr.2014.07.037","volume":"277","author":"M Politis","year":"2015","unstructured":"Politis, M. & Niccolini, F. Serotonin in Parkinson\u2019s disease. Behav. Brain Res. 277, 136\u2013145 (2015).","journal-title":"Behav. Brain Res."},{"key":"542_CR340","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1016\/bs.pbr.2020.11.001","volume":"261","author":"ER de Natale","year":"2021","unstructured":"de Natale, E. R., Wilson, H. & Politis, M. Serotonergic imaging in Parkinson\u2019s disease. Prog. Brain Res. 261, 303\u2013338 (2021).","journal-title":"Prog. Brain Res."},{"key":"542_CR341","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.pneurobio.2011.08.004","volume":"95","author":"P Huot","year":"2011","unstructured":"Huot, P., Fox, S. H. & Brotchie, J. M. The serotonergic system in Parkinson\u2019s disease. Prog. Neurobiol. 95, 163\u2013212 (2011).","journal-title":"Prog. Neurobiol."},{"key":"542_CR342","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/j.1365-2990.1983.tb00320.x","volume":"9","author":"DMA Mann","year":"1983","unstructured":"Mann, D. M. A. & Yates, P. O. Pathological basis for neurotransmitter changes in Parkinson\u2019s disease. Neuropathol. Appl. Neurobiol. 9, 3\u201319 (1983).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"542_CR343","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/0197-4580(87)90134-5","volume":"8","author":"K Jellinger","year":"1987","unstructured":"Jellinger, K. Quantitative changes in some subcortical nuclei in aging, Alzheimer\u2019s disease and Parkinson\u2019s disease. Neurobiol. Aging 8, 556\u2013561 (1987).","journal-title":"Neurobiol. Aging"},{"key":"542_CR344","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/0006-8993(90)90733-R","volume":"510","author":"GM Halliday","year":"1990","unstructured":"Halliday, G. M., Blumbergs, P. C., Cotton, R. G. H., Blessing, W. W. & Geffen, L. B. Loss of brainstem serotonin- and substance P-containing neurons in Parkinson\u2019s disease. Brain Res. 510, 104\u2013107 (1990).","journal-title":"Brain Res."},{"key":"542_CR345","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1002\/acn3.246","volume":"2","author":"C Buddhala","year":"2015","unstructured":"Buddhala, C. et al. Dopaminergic, serotonergic, and noradrenergic deficits in Parkinson disease. Ann. Clin. Transl. Neurol. 2, 949\u2013959 (2015).","journal-title":"Ann. Clin. Transl. Neurol."},{"key":"542_CR346","first-page":"120","volume":"131","author":"SJ Kish","year":"2008","unstructured":"Kish, S. J. et al. Preferential loss of serotonin markers in caudate versus putamen in Parkinson\u2019s disease. Brain 131, 120\u2013131 (2008).","journal-title":"Brain"},{"key":"542_CR347","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1016\/j.parkreldis.2011.05.012","volume":"17","author":"C B\u00e9dard","year":"2011","unstructured":"B\u00e9dard, C. et al. Serotonin and dopamine striatal innervation in Parkinson\u2019s disease and Huntington\u2019s chorea. Parkinsonism Relat. Disord. 17, 593\u2013598 (2011).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR348","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1097\/00005072-199111000-00006","volume":"50","author":"W Paulus","year":"1991","unstructured":"Paulus, W. & Jellinger, K. The neuropathologic basis of different clinical subgroups of Parkinson\u2019s disease. J. Neuropathol. Exp. Neurol. 50, 743\u2013755 (1991).","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"542_CR349","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1016\/S1474-4422(19)30140-1","volume":"18","author":"H Wilson","year":"2019","unstructured":"Wilson, H. et al. Serotonergic pathology and disease burden in the premotor and motor phase of A53T \u03b1-synuclein parkinsonism: a cross-sectional study. Lancet Neurol. 18, 748\u2013759 (2019).","journal-title":"Lancet Neurol."},{"key":"542_CR350","doi-asserted-by":"publisher","first-page":"2964","DOI":"10.1093\/brain\/awv215","volume":"138","author":"Z Qamhawi","year":"2015","unstructured":"Qamhawi, Z. et al. Clinical correlates of raphe serotonergic dysfunction in early Parkinson\u2019s disease. Brain 138, 2964\u20132973 (2015).","journal-title":"Brain"},{"key":"542_CR351","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.parkreldis.2019.03.025","volume":"77","author":"J Pasquini","year":"2020","unstructured":"Pasquini, J., Ceravolo, R., Brooks, D. J., Bonuccelli, U. & Pavese, N. Progressive loss of raphe nuclei serotonin transporter in early Parkinson\u2019s disease: a longitudinal 123I-FP-CIT SPECT study. Parkinsonism Relat. Disord. 77, 170\u2013175 (2020).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR352","doi-asserted-by":"publisher","first-page":"5976","DOI":"10.1073\/pnas.84.16.5976","volume":"84","author":"EC Hirsch","year":"1987","unstructured":"Hirsch, E. C., Graybiel, A. M., Duyckaerts, C. & Javoy-Agid, F. Neuronal loss in the pedunculopontine tegmental nucleus in Parkinson disease and in progressive supranuclear palsy. Proc. Natl Acad. Sci. USA 84, 5976\u20135980 (1987).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"542_CR353","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.parkreldis.2021.05.027","volume":"88","author":"MJ Grothe","year":"2021","unstructured":"Grothe, M. J. et al. In vivo cholinergic basal forebrain degeneration and cognition in Parkinson\u2019s disease: Imaging results from the COPPADIS study. Parkinsonism Relat. Disord. 88, 68\u201375 (2021).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR354","doi-asserted-by":"publisher","first-page":"218","DOI":"10.1002\/mds.27578","volume":"34","author":"SB S\u00e9bille","year":"2019","unstructured":"S\u00e9bille, S. B. et al. Normal and pathological neuronal distribution of the human mesencephalic locomotor region. Mov. Disord. 34, 218\u2013227 (2019).","journal-title":"Mov. Disord."},{"key":"542_CR355","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1002\/mds.28453","volume":"36","author":"J Wilson","year":"2021","unstructured":"Wilson, J. et al. Cholinergic basal forebrain volumes predict gait decline in Parkinson\u2019s disease. Mov. Disord. 36, 611\u2013621 (2021).","journal-title":"Mov. Disord."},{"key":"542_CR356","doi-asserted-by":"publisher","first-page":"1767","DOI":"10.1093\/brain\/123.9.1767","volume":"123","author":"PA Pahapill","year":"2000","unstructured":"Pahapill, P. A. & Lozano, A. M. The pedunculopontine nucleus and Parkinson\u2019s disease. Brain 123, 1767\u20131783 (2000).","journal-title":"Brain"},{"key":"542_CR357","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.parkreldis.2008.01.006","volume":"14","author":"JO Rinne","year":"2008","unstructured":"Rinne, J. O., Ma, S. Y., Lee, M. S., Collan, Y. & R\u00f6ytt\u00e4, M. Loss of cholinergic neurons in the pedunculopontine nucleus in Parkinson\u2019s disease is related to disability of the patients. Parkinsonism Relat. Disord. 14, 553\u2013557 (2008).","journal-title":"Parkinsonism Relat. Disord."},{"key":"542_CR358","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-013-0377-9","volume":"13","author":"MLTM M\u00fcller","year":"2013","unstructured":"M\u00fcller, M. L. T. M. & Bohnen, N. I. Cholinergic dysfunction in Parkinson\u2019s disease. Curr. Neurol. Neurosci. Rep. 13, 377 (2013).","journal-title":"Curr. Neurol. Neurosci. Rep."},{"key":"542_CR359","doi-asserted-by":"publisher","first-page":"104831","DOI":"10.1016\/j.nbd.2020.104831","volume":"139","author":"JB Pereira","year":"2020","unstructured":"Pereira, J. B. et al. Longitudinal degeneration of the basal forebrain predicts subsequent dementia in Parkinson\u2019s disease. Neurobiol. Dis. 139, 104831 (2020).","journal-title":"Neurobiol. Dis."},{"key":"542_CR360","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1093\/brain\/awx310","volume":"141","author":"NJ Ray","year":"2018","unstructured":"Ray, N. J. et al. In vivo cholinergic basal forebrain atrophy predicts cognitive decline in de novo Parkinson\u2019s disease. Brain 141, 165\u2013176 (2018).","journal-title":"Brain"},{"key":"542_CR361","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1136\/jnnp-2019-320450","volume":"90","author":"MJ Barrett","year":"2019","unstructured":"Barrett, M. J. et al. Lower volume, more impairment: reduced cholinergic basal forebrain grey matter density is associated with impaired cognition in Parkinson disease. J. Neurol. Neurosurg. Psychiatry 90, 1251\u20131256 (2019).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"542_CR362","doi-asserted-by":"publisher","first-page":"209","DOI":"10.1016\/j.expneurol.2015.11.004","volume":"275","author":"M Bensaid","year":"2016","unstructured":"Bensaid, M., Michel, P. P., Clark, S. D., Hirsch, E. C. & Fran\u00e7ois, C. Role of pedunculopontine cholinergic neurons in the vulnerability of nigral dopaminergic neurons in Parkinson\u2019s disease. Exp. Neurol. 275, 209\u2013219 (2016).","journal-title":"Exp. Neurol."},{"key":"542_CR363","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.nbd.2018.08.017","volume":"128","author":"C Tubert","year":"2019","unstructured":"Tubert, C., Galtieri, D. & Surmeier, D. J. The pedunclopontine nucleus and Parkinson\u2019s disease. Neurobiol. Dis. 128, 3\u20138 (2019).","journal-title":"Neurobiol. Dis."}],"container-title":["Nature Reviews Neuroscience"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41583-021-00542-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41583-021-00542-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41583-021-00542-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T04:00:30Z","timestamp":1722916830000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41583-021-00542-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,14]]},"references-count":363,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,2]]}},"alternative-id":["542"],"URL":"https:\/\/doi.org\/10.1038\/s41583-021-00542-9","relation":{},"ISSN":["1471-003X","1471-0048"],"issn-type":[{"value":"1471-003X","type":"print"},{"value":"1471-0048","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,14]]},"assertion":[{"value":"12 November 2021","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2021","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}