{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T05:26:09Z","timestamp":1774329969604,"version":"3.50.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T00:00:00Z","timestamp":1658880000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Clin Auton Res"],"published-print":{"date-parts":[[2022,8]]},"DOI":"10.1007\/s10286-022-00882-1","type":"journal-article","created":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T13:00:05Z","timestamp":1659099605000},"page":"291-297","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Recent advances in establishing fluid biomarkers for the diagnosis and differentiation of alpha-synucleinopathies \u2013 a mini review"],"prefix":"10.1007","volume":"32","author":[{"given":"Wolfgang","family":"Singer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"882_CR1","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1056\/NEJMra1311488","volume":"372","author":"A Fanciulli","year":"2015","unstructured":"Fanciulli A, Wenning GK (2015) Multiple-system atrophy. N Engl J Med 372:249\u2013263","journal-title":"N Engl J Med"},{"key":"882_CR2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/S0140-6736(14)61393-3","volume":"386","author":"LV Kalia","year":"2015","unstructured":"Kalia LV, Lang AE (2015) Parkinson\u2019s disease. Lancet 386:896\u2013912","journal-title":"Lancet"},{"key":"882_CR3","doi-asserted-by":"publisher","first-page":"980","DOI":"10.1212\/WNL.56.7.980","volume":"56","author":"H Kaufmann","year":"2001","unstructured":"Kaufmann H, Hague K, Perl D (2001) Accumulation of alpha-synuclein in autonomic nerves in pure autonomic failure. Neurology 56:980\u2013981","journal-title":"Neurology"},{"key":"882_CR4","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/0022-510X(89)90219-0","volume":"94","author":"MI Papp","year":"1989","unstructured":"Papp MI, Kahn JE, Lantos PL (1989) Glial cytoplasmic inclusions in the CNS of patients with multiple system atrophy (striatonigral degeneration, olivopontocerebellar atrophy and Shy-Drager syndrome). J Neurol Sci 94:79\u2013100","journal-title":"J Neurol Sci"},{"key":"882_CR5","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/S0140-6736(15)00462-6","volume":"386","author":"Z Walker","year":"2015","unstructured":"Walker Z, Possin KL, Boeve BF, Aarsland D (2015) Lewy body dementias. Lancet 386:1683\u20131697","journal-title":"Lancet"},{"issue":"7","key":"882_CR6","first-page":"e889","volume":"95","author":"EA Coon","year":"2020","unstructured":"Coon EA, Mandrekar JN, Berini SE et al (2020) Predicting phenoconversion in pure autonomic failure. Neuroogy 95(7):e889\u2013e897","journal-title":"Neuroogy"},{"key":"882_CR7","first-page":"72","volume":"26","author":"EA Coon","year":"2020","unstructured":"Coon EA, Singer W (2020) Synucleinopathies. Continu (Minneap Minn) 26:72\u201392","journal-title":"Continu (Minneap Minn)"},{"key":"882_CR8","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1002\/ana.24877","volume":"81","author":"H Kaufmann","year":"2017","unstructured":"Kaufmann H, Norcliffe-Kaufmann L, Palma JA et al (2017) Natural history of pure autonomic failure: A United States prospective cohort. Ann Neurol 81:287\u2013297","journal-title":"Ann Neurol"},{"key":"882_CR9","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1212\/WNL.0000000000003737","volume":"88","author":"W Singer","year":"2017","unstructured":"Singer W, Berini SE, Sandroni P et al (2017) Pure autonomic failure: Predictors of conversion to clinical CNS involvement. Neurology 88:1129\u20131136","journal-title":"Neurology"},{"key":"882_CR10","doi-asserted-by":"publisher","first-page":"2087","DOI":"10.1016\/j.mayocp.2019.03.009","volume":"94","author":"EA Coon","year":"2019","unstructured":"Coon EA, Singer W, Low PA (2019) Pure autonomic failure. Mayo Clin Proc 94:2087\u20132098","journal-title":"Mayo Clin Proc"},{"key":"882_CR11","doi-asserted-by":"publisher","first-page":"763","DOI":"10.1016\/j.sleep.2012.09.001","volume":"14","author":"RB Postuma","year":"2013","unstructured":"Postuma RB, Gagnon JF, Montplaisir J (2013) Rapid eye movement sleep behavior disorder as a biomarker for neurodegeneration: the past 10\u00a0years. Sleep Med 14:763\u2013767","journal-title":"Sleep Med"},{"key":"882_CR12","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1365-2990.2007.00907.x","volume":"33","author":"JQ Trojanowski","year":"2007","unstructured":"Trojanowski JQ, Revesz T (2007) Proposed neuropathological criteria for the post mortem diagnosis of multiple system atrophy. Neuropathol Appl Neurobiol 33:615\u2013620","journal-title":"Neuropathol Appl Neurobiol"},{"key":"882_CR13","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s004010050693","volume":"94","author":"K Hague","year":"1997","unstructured":"Hague K, Lento P, Morgello S, Caro S, Kaufmann H (1997) The distribution of Lewy bodies in pure autonomic failure: autopsy findings and review of the literature. Acta Neuropathol 94:192\u2013196","journal-title":"Acta Neuropathol"},{"key":"882_CR14","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41586-018-0104-4","volume":"557","author":"C Peng","year":"2018","unstructured":"Peng C, Gathagan RJ, Covell DJ et al (2018) Cellular milieu imparts distinct pathological alpha-synuclein strains in alpha-synucleinopathies. Nature 557:558\u2013563","journal-title":"Nature"},{"key":"882_CR15","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41586-020-1984-7","volume":"578","author":"M Shahnawaz","year":"2020","unstructured":"Shahnawaz M, Mukherjee A, Pritzkow S et al (2020) Discriminating alpha-synuclein strains in Parkinson\u2019s disease and multiple system atrophy. Nature 578:273\u2013277","journal-title":"Nature"},{"key":"882_CR16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00401-021-02311-5","volume":"142","author":"AL Woerman","year":"2021","unstructured":"Woerman AL (2021) Strain diversity in neurodegenerative disease: an argument for a personalized medicine approach to diagnosis and treatment. Acta Neuropathol 142:1\u20133","journal-title":"Acta Neuropathol"},{"key":"882_CR17","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1093\/brain\/awf080","volume":"125","author":"AJ Hughes","year":"2002","unstructured":"Hughes AJ, Daniel SE, Ben-Shlomo Y, Lees AJ (2002) The accuracy of diagnosis of parkinsonian syndromes in a specialist movement disorder service. Brain 125:861\u2013870","journal-title":"Brain"},{"key":"882_CR18","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1212\/WNL.0000000000001807","volume":"85","author":"S Koga","year":"2015","unstructured":"Koga S, Aoki N, Uitti RJ et al (2015) When DLB, PD, and PSP masquerade as MSA: an autopsy study of 134 patients. Neurology 85:404\u2013412","journal-title":"Neurology"},{"key":"882_CR19","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1002\/mds.26715","volume":"31","author":"HJ Huppertz","year":"2016","unstructured":"Huppertz HJ, Moller L, Sudmeyer M et al (2016) Differentiation of neurodegenerative parkinsonian syndromes by volumetric magnetic resonance imaging analysis and support vector machine classification. Mov Disord 31:1506\u20131517","journal-title":"Mov Disord"},{"key":"882_CR20","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1007\/s00415-011-6280-x","volume":"259","author":"FJ Meijer","year":"2012","unstructured":"Meijer FJ, Aerts MB, Abdo WF et al (2012) Contribution of routine brain MRI to the differential diagnosis of parkinsonism: a 3\u00a0year prospective follow-up study. J Neurol 259:929\u2013935","journal-title":"J Neurol"},{"key":"882_CR21","doi-asserted-by":"publisher","first-page":"572976","DOI":"10.3389\/fneur.2020.572976","volume":"11","author":"U Saeed","year":"2020","unstructured":"Saeed U, Lang AE, Masellis M (2020) Neuroimaging advances in Parkinson\u2019s disease and atypical parkinsonian syndromes. Front Neurol 11:572976","journal-title":"Front Neurol"},{"key":"882_CR22","doi-asserted-by":"publisher","first-page":"e112638","DOI":"10.1371\/journal.pone.0112638","volume":"9","author":"A Worker","year":"2014","unstructured":"Worker A, Blain C, Jarosz J et al (2014) Diffusion tensor imaging of Parkinson\u2019s disease, multiple system atrophy and progressive supranuclear palsy: a tract-based spatial statistics study. PLoS ONE 9:e112638","journal-title":"PLoS ONE"},{"key":"882_CR23","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1212\/01.wnl.0000227891.25592.8c","volume":"67","author":"WF Abdo","year":"2006","unstructured":"Abdo WF, van de Warrenburg BP, Munneke M et al (2006) CSF analysis differentiates multiple-system atrophy from idiopathic late-onset cerebellar ataxia. Neurology 67:474\u2013479","journal-title":"Neurology"},{"key":"882_CR24","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1001\/archneurol.2012.1654","volume":"69","author":"S Hall","year":"2012","unstructured":"Hall S, Ohrfelt A, Constantinescu R et al (2012) Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and\/or parkinsonian disorders. Arch Neurol 69:1445\u20131452","journal-title":"Arch Neurol"},{"key":"882_CR25","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.3233\/JAD-190615","volume":"72","author":"SY Wang","year":"2019","unstructured":"Wang SY, Chen W, Xu W et al (2019) Neurofilament light chain in cerebrospinal fluid and blood as a biomarker for neurodegenerative diseases: a systematic review and meta-analysis. J Alzheimers Dis 72:1353\u20131361","journal-title":"J Alzheimers Dis"},{"key":"882_CR26","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1016\/j.neurobiolaging.2006.03.010","volume":"28","author":"WF Abdo","year":"2007","unstructured":"Abdo WF, Bloem BR, Van Geel WJ, Esselink RA, Verbeek MM (2007) CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson\u2019s disease. Neurobiol Aging 28:742\u2013747","journal-title":"Neurobiol Aging"},{"key":"882_CR27","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/j.parkreldis.2007.02.002","volume":"13","author":"WF Abdo","year":"2007","unstructured":"Abdo WF, van de Warrenburg BP, Kremer HP, Bloem BR, Verbeek MM (2007) CSF biomarker profiles do not differentiate between the cerebellar and parkinsonian phenotypes of multiple system atrophy. Parkinsonism Relat Disord 13:480\u2013482","journal-title":"Parkinsonism Relat Disord"},{"issue":"3","key":"882_CR28","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1002\/ana.25824","volume":"88","author":"W Singer","year":"2020","unstructured":"Singer W, Schmeichel AM, Shahnawaz M et al (2020) Alpha-synuclein oligomers and neurofilament light chain in spinal fluid differentiate multiple system atrophy from lewy body synucleinopathies. Ann Neurol 88(3):503\u2013512","journal-title":"Ann Neurol"},{"key":"882_CR29","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1002\/ana.26089","volume":"89","author":"W Singer","year":"2021","unstructured":"Singer W, Schmeichel AM, Shahnawaz M et al (2021) Alpha-synuclein oligomers and neurofilament light chain predict phenoconversion of pure autonomic failure. Ann Neurol 89:1212\u20131220","journal-title":"Ann Neurol"},{"key":"882_CR30","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1002\/ana.23746","volume":"73","author":"LV Kalia","year":"2013","unstructured":"Kalia LV, Kalia SK, McLean PJ, Lozano AM, Lang AE (2013) Alpha-synuclein oligomers and clinical implications for Parkinson disease. Ann Neurol 73:155\u2013169","journal-title":"Ann Neurol"},{"key":"882_CR31","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1002\/ana.22311","volume":"69","author":"M Shi","year":"2011","unstructured":"Shi M, Bradner J, Hancock AM et al (2011) Cerebrospinal fluid biomarkers for Parkinson disease diagnosis and progression. Ann Neurol 69:570\u2013580","journal-title":"Ann Neurol"},{"key":"882_CR32","doi-asserted-by":"publisher","first-page":"1766","DOI":"10.1212\/WNL.0b013e3181fd613b","volume":"75","author":"T Tokuda","year":"2010","unstructured":"Tokuda T, Qureshi MM, Ardah MT et al (2010) Detection of elevated levels of alpha-synuclein oligomers in CSF from patients with Parkinson disease. Neurology 75:1766\u20131772","journal-title":"Neurology"},{"key":"882_CR33","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/j.bbrc.2006.08.024","volume":"349","author":"T Tokuda","year":"2006","unstructured":"Tokuda T, Salem SA, Allsop D et al (2006) Decreased alpha-synuclein in cerebrospinal fluid of aged individuals and subjects with Parkinson\u2019s disease. Biochem Biophys Res Commun 349:162\u2013166","journal-title":"Biochem Biophys Res Commun"},{"key":"882_CR34","doi-asserted-by":"publisher","first-page":"e1867","DOI":"10.1371\/journal.pone.0001867","volume":"3","author":"TF Outeiro","year":"2008","unstructured":"Outeiro TF, Putcha P, Tetzlaff JE et al (2008) Formation of toxic oligomeric alpha-synuclein species in living cells. PLoS ONE 3:e1867","journal-title":"PLoS ONE"},{"key":"882_CR35","doi-asserted-by":"publisher","first-page":"17962","DOI":"10.1074\/jbc.M802283200","volume":"283","author":"JE Tetzlaff","year":"2008","unstructured":"Tetzlaff JE, Putcha P, Outeiro TF et al (2008) CHIP targets toxic alpha-Synuclein oligomers for degradation. J Biol Chem 283:17962\u201317968","journal-title":"J Biol Chem"},{"key":"882_CR36","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1001\/jamaneurol.2016.4547","volume":"74","author":"M Shahnawaz","year":"2017","unstructured":"Shahnawaz M, Tokuda T, Waragai M et al (2017) Development of a biochemical diagnosis of parkinson disease by detection of alpha-synuclein misfolded aggregates in cerebrospinal fluid. JAMA Neurol 74:163\u2013172","journal-title":"JAMA Neurol"},{"key":"882_CR37","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1002\/mds.27646","volume":"34","author":"UJ Kang","year":"2019","unstructured":"Kang UJ, Boehme AK, Fairfoul G et al (2019) Comparative study of cerebrospinal fluid alpha-synuclein seeding aggregation assays for diagnosis of Parkinson\u2019s disease. Mov Disord 34:536\u2013544","journal-title":"Mov Disord"},{"key":"882_CR38","doi-asserted-by":"publisher","first-page":"E5308","DOI":"10.1073\/pnas.1514475112","volume":"112","author":"SB Prusiner","year":"2015","unstructured":"Prusiner SB, Woerman AL, Mordes DA et al (2015) Evidence for alpha-synuclein prions causing multiple system atrophy in humans with parkinsonism. Proc Natl Acad Sci U S A 112:E5308-5317","journal-title":"Proc Natl Acad Sci U S A"},{"key":"882_CR39","doi-asserted-by":"publisher","first-page":"1332","DOI":"10.1038\/s41593-018-0235-9","volume":"21","author":"C Soto","year":"2018","unstructured":"Soto C, Pritzkow S (2018) Protein misfolding, aggregation, and conformational strains in neurodegenerative diseases. Nat Neurosci 21:1332\u20131340","journal-title":"Nat Neurosci"},{"key":"882_CR40","doi-asserted-by":"publisher","first-page":"E4949","DOI":"10.1073\/pnas.1513426112","volume":"112","author":"AL Woerman","year":"2015","unstructured":"Woerman AL, Stohr J, Aoyagi A et al (2015) Propagation of prions causing synucleinopathies in cultured cells. Proc Natl Acad Sci U S A 112:E4949-4958","journal-title":"Proc Natl Acad Sci U S A"},{"key":"882_CR41","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1016\/S0166-2236(02)02195-1","volume":"25","author":"C Soto","year":"2002","unstructured":"Soto C, Saborio GP, Anderes L (2002) Cyclic amplification of protein misfolding: application to prion-related disorders and beyond. Trends Neurosci 25:390\u2013394","journal-title":"Trends Neurosci"},{"key":"882_CR42","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1002\/acn3.338","volume":"3","author":"G Fairfoul","year":"2016","unstructured":"Fairfoul G, McGuire LI, Pal S et al (2016) Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies. Ann Clin Transl Neurol 3:812\u2013818","journal-title":"Ann Clin Transl Neurol"},{"key":"882_CR43","doi-asserted-by":"publisher","first-page":"584","DOI":"10.1093\/brain\/awab431","volume":"145","author":"I Poggiolini","year":"2022","unstructured":"Poggiolini I, Gupta V, Lawton M et al (2022) Diagnostic value of cerebrospinal fluid alpha-synuclein seed quantification in synucleinopathies. Brain 145:584\u2013595","journal-title":"Brain"},{"issue":"9","key":"882_CR44","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1007\/s00401-020-02160-8","volume":"140","author":"M Rossi","year":"2020","unstructured":"Rossi M, Candelise N, Baiardi S et al (2020) Ultrasensitive RT-QuIC assay with high sensitivity and specificity for lewy body-associated synucleinopathies. Acta Neuropathol 140(9):49\u201362","journal-title":"Acta Neuropathol"},{"key":"882_CR45","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40035-022-00283-4","volume":"11","author":"I Martinez-Valbuena","year":"2022","unstructured":"Martinez-Valbuena I, Visanji NP, Kim A et al (2022) Alpha-synuclein seeding shows a wide heterogeneity in multiple system atrophy. Transl Neurodegener 11:7","journal-title":"Transl Neurodegener"},{"key":"882_CR46","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S1474-4422(20)30449-X","volume":"20","author":"A Iranzo","year":"2021","unstructured":"Iranzo A, Fairfoul G, Ayudhaya ACN et al (2021) Detection of alpha-synuclein in CSF by RT-QuIC in patients with isolated rapid-eye-movement sleep behaviour disorder: a longitudinal observational study. Lancet Neurol 20:203\u2013212","journal-title":"Lancet Neurol"},{"key":"882_CR47","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00401-021-02324-0","volume":"142","author":"S Dutta","year":"2021","unstructured":"Dutta S, Hornung S, Kruayatidee A et al (2021) alpha-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson\u2019s disease from multiple system atrophy. Acta Neuropathol 142:495\u2013511","journal-title":"Acta Neuropathol"},{"key":"882_CR48","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1136\/jnnp-2019-322588","volume":"91","author":"C Jiang","year":"2020","unstructured":"Jiang C, Hopfner F, Katsikoudi A et al (2020) Serum neuronal exosomes predict and differentiate Parkinson\u2019s disease from atypical parkinsonism. J Neurol Neurosurg Psychiatry 91:720\u2013729","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"882_CR49","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1093\/brain\/awaa110","volume":"143","author":"Z Yu","year":"2020","unstructured":"Yu Z, Shi M, Stewart T et al (2020) Reduced oligodendrocyte exosome secretion in multiple system atrophy involves SNARE dysfunction. Brain 143:1780\u20131797","journal-title":"Brain"}],"container-title":["Clinical Autonomic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10286-022-00882-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10286-022-00882-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10286-022-00882-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T10:07:49Z","timestamp":1660644469000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10286-022-00882-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":49,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["882"],"URL":"https:\/\/doi.org\/10.1007\/s10286-022-00882-1","relation":{},"ISSN":["0959-9851","1619-1560"],"issn-type":[{"value":"0959-9851","type":"print"},{"value":"1619-1560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]},"assertion":[{"value":"14 July 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 July 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 July 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}