{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,11]],"date-time":"2026-11-11T07:05:27Z","timestamp":1794380727515,"version":"4.9.0"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Biogen (Cambridge, MA, USA) sponsored this study and provided medical writing and editorial support for the development of this publication."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2021,8]]},"DOI":"10.1038\/s41591-021-01455-x","type":"journal-article","created":{"date-parts":[[2021,8,12]],"date-time":"2021-08-12T12:04:14Z","timestamp":1628769854000},"page":"1451-1457","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":146,"title":["Safety and efficacy of anti-tau monoclonal antibody gosuranemab in progressive supranuclear palsy: a phase 2, randomized, placebo-controlled trial"],"prefix":"10.1038","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7786-5825","authenticated-orcid":false,"given":"Tien","family":"Dam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam L.","family":"Boxer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence I.","family":"Golbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-6187","authenticated-orcid":false,"given":"G\u00fcnter U.","family":"H\u00f6glinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5473-3774","authenticated-orcid":false,"given":"Huw R.","family":"Morris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3485-3445","authenticated-orcid":false,"given":"Irene","family":"Litvan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony E.","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Christophe","family":"Corvol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Aiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Grundman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beth","family":"Tidemann-Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Kupferman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristine","family":"Harper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6620-0564","authenticated-orcid":false,"given":"Kubra","family":"Kamisoglu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Wald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle L.","family":"Graham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liz","family":"Gedney","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"O\u2019Gorman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha Budd","family":"Haeberlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"PASSPORT Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,8,12]]},"reference":[{"key":"1455_CR1","doi-asserted-by":"publisher","first-page":"552","DOI":"10.1016\/S1474-4422(17)30157-6","volume":"16","author":"AL Boxer","year":"2017","unstructured":"Boxer, A. L. et al. Advances in progressive supranuclear palsy: new diagnostic criteria, biomarkers, and therapeutic approaches. Lancet Neurol. 16, 552\u2013563 (2017).","journal-title":"Lancet Neurol."},{"key":"1455_CR2","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/mds.26987","volume":"32","author":"GU H\u00f6glinger","year":"2017","unstructured":"H\u00f6glinger, G. U. et al. Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov. Disord. 32, 853\u2013864 (2017).","journal-title":"Mov. Disord."},{"key":"1455_CR3","doi-asserted-by":"publisher","first-page":"1727","DOI":"10.1007\/s00415-019-09324-x","volume":"266","author":"M Picillo","year":"2019","unstructured":"Picillo, M. et al. Motor, cognitive and behavioral differences in MDS PSP phenotypes. J. Neurol. 266, 1727\u20131735 (2019).","journal-title":"J. Neurol."},{"key":"1455_CR4","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1055\/s-0034-1381736","volume":"34","author":"LI Golbe","year":"2014","unstructured":"Golbe, L. I. Progressive supranuclear palsy. Semin. Neurol. 34, 151\u2013159 (2014).","journal-title":"Semin. Neurol."},{"key":"1455_CR5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1212\/WNL.47.1.1","volume":"47","author":"I Litvan","year":"1996","unstructured":"Litvan, I. et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele\u2013Richardson\u2013Olszewski syndrome): report of the NINDS-SPSP international workshop. Neurology 47, 1\u20139 (1996).","journal-title":"Neurology"},{"key":"1455_CR6","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1093\/brain\/awm032","volume":"130","author":"LI Golbe","year":"2007","unstructured":"Golbe, L. I. & Ohman-Strickland, P. A. A clinical rating scale for progressive supranuclear palsy. Brain 130, 1552\u20131565 (2007).","journal-title":"Brain"},{"key":"1455_CR7","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1002\/mds.25327","volume":"28","author":"G Respondek","year":"2013","unstructured":"Respondek, G. et al. Accuracy of the National Institute for Neurological Disorders and Stroke\/Society for Progressive Supranuclear Palsy and neuroprotection and natural history in Parkinson plus syndromes criteria for the diagnosis of progressive supranuclear palsy. Mov. Disord. 28, 504\u2013509 (2013).","journal-title":"Mov. Disord."},{"key":"1455_CR8","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1097\/WCO.0b013e32833be924","volume":"23","author":"DW Dickson","year":"2010","unstructured":"Dickson, D. W., Ahmed, Z., Algom, A. A., Tsuboi, Y. & Josephs, K. A. Neuropathology of variants of progressive supranuclear palsy. Curr. Opin. Neurol. 23, 394\u2013400 (2010).","journal-title":"Curr. Opin. Neurol."},{"key":"1455_CR9","doi-asserted-by":"publisher","first-page":"a009258","DOI":"10.1101\/cshperspect.a009258","volume":"2","author":"DW Dickson","year":"2012","unstructured":"Dickson, D. W. Parkinson\u2019s disease and parkinsonism: neuropathology. Cold Spring Harb. Perspect. Med. 2, a009258 (2012).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"1455_CR10","doi-asserted-by":"publisher","first-page":"645","DOI":"10.3390\/ijms19030645","volume":"19","author":"A Fuster-Matanzo","year":"2018","unstructured":"Fuster-Matanzo, A., Hern\u00e1ndez, F. & \u00c1vila, J. Tau spreading mechanisms; implications for dysfunctional tauopathies. Int. J. Mol. Sci. 19, 645 (2018).","journal-title":"Int. J. Mol. Sci."},{"key":"1455_CR11","doi-asserted-by":"publisher","first-page":"e76523","DOI":"10.1371\/journal.pone.0076523","volume":"8","author":"JE Meredith Jr.","year":"2013","unstructured":"Meredith, J. E. Jr. et al. Characterization of novel CSF tau and ptau biomarkers for Alzheimer\u2019s disease. PLoS One 8, e76523 (2013).","journal-title":"PLoS One"},{"key":"1455_CR12","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.neurobiolaging.2014.09.007","volume":"36","author":"J Bright","year":"2015","unstructured":"Bright, J. et al. Human secreted tau increases amyloid-beta production. Neurobiol. Aging 36, 693\u2013709 (2015).","journal-title":"Neurobiol. Aging"},{"key":"1455_CR13","doi-asserted-by":"publisher","first-page":"1284","DOI":"10.1016\/j.neuron.2018.02.015","volume":"97","author":"C Sato","year":"2018","unstructured":"Sato, C. et al. Tau kinetics in neurons and the human central nervous system. Neuron 97, 1284\u20131298 (2018).","journal-title":"Neuron"},{"key":"1455_CR14","doi-asserted-by":"publisher","first-page":"9535","DOI":"10.1073\/pnas.1301175110","volume":"110","author":"F Clavaguera","year":"2013","unstructured":"Clavaguera, F. et al. Brain homogenates from human tauopathies induce tau inclusions in mouse brain. Proc. Natl Acad. Sci. USA 110, 9535\u20139540 (2013).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"1455_CR15","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1523\/JNEUROSCI.2824-07.2008","volume":"28","author":"MM Mocanu","year":"2008","unstructured":"Mocanu, M. M. et al. The potential for beta-structure in the repeat domain of tau protein determines aggregation, synaptic decay, neuronal loss, and coassembly with endogenous tau in inducible mouse models of tauopathy. J. Neurosci. 28, 737\u2013748 (2008).","journal-title":"J. Neurosci."},{"key":"1455_CR16","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1016\/j.neuron.2014.04.047","volume":"82","author":"DW Sanders","year":"2014","unstructured":"Sanders, D. W. et al. Distinct tau prion strains propagate in cells and mice and define different tauopathies. Neuron 82, 1271\u20131288 (2014).","journal-title":"Neuron"},{"key":"1455_CR17","unstructured":"Golonzhka, O. et al. Functional characterization of anti-tau monoclonal antibody BIIB092. Presented at 14th International Conference on Alzheimer\u2019s and Parkinson\u2019s Diseases (26\u201331 March, 2019, Lisbon, Portugal)."},{"key":"1455_CR18","doi-asserted-by":"publisher","first-page":"1288","DOI":"10.1016\/j.jalz.2019.06.3697","volume":"15","author":"J Czerkowicz","year":"2019","unstructured":"Czerkowicz, J. et al. Pharmacokinetic and target engagement analysis of anti-tau antibody gosuranemab [BIIB092] in cynomolgus monkey central nervous system fluid compartments. Alzheimers Dement. 15, 1288\u20131289 (2019).","journal-title":"Alzheimers Dement."},{"key":"1455_CR19","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1016\/j.trci.2018.10.007","volume":"4","author":"IA Qureshi","year":"2018","unstructured":"Qureshi, I. A. et al. A randomized, single ascending dose study of intravenous BIIB092 in healthy participants. Alzheimers Dement. 4, 746\u2013755 (2018).","journal-title":"Alzheimers Dement."},{"key":"1455_CR20","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/S1474-4422(19)30139-5","volume":"18","author":"AL Boxer","year":"2019","unstructured":"Boxer, A. L. et al. Safety of the tau-directed monoclonal antibody BIIB092 in progressive supranuclear palsy: a randomised, placebo-controlled, multiple ascending dose phase 1b trial. Lancet Neurol. 18, 549\u2013558 (2019).","journal-title":"Lancet Neurol."},{"key":"1455_CR21","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1016\/S1474-4422(14)70088-2","volume":"13","author":"AL Boxer","year":"2014","unstructured":"Boxer, A. L. et al. Davunetide in patients with progressive supranuclear palsy: a randomised, double-blind, placebo-controlled phase 2\/3 trial. Lancet Neurol. 13, 676\u2013685 (2014).","journal-title":"Lancet Neurol."},{"key":"1455_CR22","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.parkreldis.2005.06.003","volume":"11","author":"S Papapetropoulos","year":"2005","unstructured":"Papapetropoulos, S., Singer, C., McCorquodale, D., Gonzalez, J. & Mash, D. C. Cause, seasonality of death and co-morbidities in progressive supranuclear palsy (PSP). Parkinsonism Relat. Disord. 11, 459\u2013463 (2005).","journal-title":"Parkinsonism Relat. Disord."},{"key":"1455_CR23","doi-asserted-by":"publisher","first-page":"842","DOI":"10.1002\/mds.26973","volume":"32","author":"GU H\u00f6glinger","year":"2017","unstructured":"H\u00f6glinger, G. U. et al. Longitudinal magnetic resonance imaging in progressive supranuclear palsy: a new combined score for clinical trials. Mov. Disord. 32, 842\u2013852 (2017).","journal-title":"Mov. Disord."},{"key":"1455_CR24","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1002\/mds.27038","volume":"32","author":"JL Whitwell","year":"2017","unstructured":"Whitwell, J. L. et al. Radiological biomarkers for diagnosis in PSP: where are we and where do we need to be? Mov. Disord. 32, 955\u2013971 (2017).","journal-title":"Mov. Disord."},{"key":"1455_CR25","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/mds.25437","volume":"28","author":"KA Josephs","year":"2013","unstructured":"Josephs, K. A. et al. Modeling trajectories of regional volume loss in progressive supranuclear palsy. Mov. Disord. 28, 1117\u20131124 (2013).","journal-title":"Mov. Disord."},{"key":"1455_CR26","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.parkreldis.2016.04.006","volume":"28","author":"RM Tsai","year":"2016","unstructured":"Tsai, R. M. et al. Clinical correlates of longitudinal brain atrophy in progressive supranuclear palsy. Parkinsonism Relat. Disord. 28, 29\u201335 (2016).","journal-title":"Parkinsonism Relat. Disord."},{"key":"1455_CR27","doi-asserted-by":"publisher","first-page":"470","DOI":"10.1002\/mds.25824","volume":"29","author":"E Tolosa","year":"2014","unstructured":"Tolosa, E. et al. A phase 2 trial of the GSK-3 inhibitor tideglusib in progressive supranuclear palsy. Mov. Disord. 29, 470\u2013478 (2014).","journal-title":"Mov. Disord."},{"key":"1455_CR28","doi-asserted-by":"publisher","first-page":"S233","DOI":"10.1212\/WNL.47.6_Suppl_4.233S","volume":"47","author":"A Doble","year":"1996","unstructured":"Doble, A. The pharmacology and mechanism of action of riluzole. Neurology 47, S233\u2013S241 (1996).","journal-title":"Neurology"},{"key":"1455_CR29","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1093\/brain\/awn291","volume":"132","author":"G Bensimon","year":"2009","unstructured":"Bensimon, G. et al. Riluzole treatment, survival and diagnostic criteria in Parkinson plus disorders: the NNIPPS study. Brain 132, 156\u2013171 (2009).","journal-title":"Brain"},{"key":"1455_CR30","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1097\/WCO.0000000000000836","volume":"33","author":"PA Vaswani","year":"2020","unstructured":"Vaswani, P. A. & Olsen, A. L. Immunotherapy in progressive supranuclear palsy. Curr. Opin. Neurol. 33, 527\u2013533 (2020).","journal-title":"Curr. Opin. Neurol."},{"key":"1455_CR31","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1212\/01.wnl.0000223826.84080.97","volume":"67","author":"A Schrag","year":"2006","unstructured":"Schrag, A. et al. Measuring quality of life in PSP: the PSP-QoL. Neurology 67, 39\u201344 (2006).","journal-title":"Neurology"},{"key":"1455_CR32","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1002\/mds.22340","volume":"23","author":"CG Goetz","year":"2008","unstructured":"Goetz, C. G. et al. Movement Disorder Society-sponsored revision of the Unified Parkinson\u2019s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov. Disord. 23, 2129\u20132170 (2008).","journal-title":"Mov. Disord."},{"key":"1455_CR33","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/j.parkreldis.2019.10.012","volume":"69","author":"A Shoeibi","year":"2019","unstructured":"Shoeibi, A. et al. Are the International Parkinson disease and Movement Disorder Society progressive supranuclear palsy (IPMDS-PSP) diagnostic criteria accurate enough to differentiate common PSP phenotypes? Parkinsonism Relat. Disord. 69, 34\u201339 (2019).","journal-title":"Parkinsonism Relat. Disord."},{"key":"1455_CR34","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.1002\/mds.26054","volume":"29","author":"G Respondek","year":"2014","unstructured":"Respondek, G. et al. The phenotypic spectrum of progressive supranuclear palsy: a retrospective multicenter study of 100 definite cases. Mov. Disord. 29, 1758\u20131766 (2014).","journal-title":"Mov. Disord."},{"key":"1455_CR35","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.parkreldis.2014.10.026","volume":"21","author":"P Mart\u00ednez-Mart\u00edn","year":"2015","unstructured":"Mart\u00ednez-Mart\u00edn, P. et al. Parkinson\u2019s disease severity levels and MDS-Unified Parkinson\u2019s Disease Rating Scale. Parkinsonism Relat. Disord. 21, 50\u201354 (2015).","journal-title":"Parkinsonism Relat. Disord."},{"key":"1455_CR36","first-page":"28","volume":"4","author":"J Busner","year":"2007","unstructured":"Busner, J. & Targum, S. D. The clinical global impressions scale: applying a research tool in clinical practice. Psychiatry 4, 28\u201337 (2007).","journal-title":"Psychiatry"},{"key":"1455_CR37","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1002\/mdc3.12678","volume":"5","author":"M Mamarabadi","year":"2018","unstructured":"Mamarabadi, M., Razjouyan, H. & Golbe, L. I. Is the latency from progressive supranuclear palsy onset to diagnosis improving? Mov. Disord. Clin. Pract. 5, 603\u2013606 (2018).","journal-title":"Mov. Disord. Clin. Pract."},{"key":"1455_CR38","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1111\/j.1444-0938.2010.00504.x","volume":"94","author":"RA Armstrong","year":"2011","unstructured":"Armstrong, R. A. Visual signs and symptoms of progressive supranuclear palsy. Clin. Exp. Optom. 94, 150\u2013160 (2011).","journal-title":"Clin. Exp. Optom."},{"key":"1455_CR39","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1002\/mds.27034","volume":"32","author":"G Respondek","year":"2017","unstructured":"Respondek, G. et al. Which ante mortem clinical features predict progressive supranuclear palsy pathology? Mov. Disord. 32, 995\u20131005 (2017).","journal-title":"Mov. Disord."},{"key":"1455_CR40","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.1002\/mds.27619","volume":"34","author":"F Ali","year":"2019","unstructured":"Ali, F. et al. Sensitivity and specificity of diagnostic criteria for progressive supranuclear palsy. Mov. Disord. 34, 1144\u20131153 (2019).","journal-title":"Mov. Disord."},{"key":"1455_CR41","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/ng.859","volume":"43","author":"GU H\u00f6glinger","year":"2011","unstructured":"H\u00f6glinger, G. U. et al. Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy. Nat. Genet. 43, 699\u2013705 (2011).","journal-title":"Nat. Genet."},{"key":"1455_CR42","doi-asserted-by":"publisher","first-page":"105120","DOI":"10.1016\/j.nbd.2020.105120","volume":"146","author":"R Sopko","year":"2020","unstructured":"Sopko, R. et al. Characterization of tau binding by gosuranemab. Neurobiol. Dis. 146, 105120 (2020).","journal-title":"Neurobiol. Dis."},{"key":"1455_CR43","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.neurobiolaging.2014.09.007","volume":"36","author":"J Bright","year":"2015","unstructured":"Bright, J. et al. Human secreted tau increases amyloid-beta production. Neurobiol. Aging 36, 693\u2013709 (2015).","journal-title":"Neurobiol. Aging"},{"key":"1455_CR44","doi-asserted-by":"publisher","first-page":"4842","DOI":"10.1016\/j.febslet.2006.07.078","volume":"580","author":"A G\u00f3mez-Ramos","year":"2006","unstructured":"G\u00f3mez-Ramos, A., D\u00edaz-Hern\u00e1ndez, M., Cuadros, R., Hern\u00e1ndez, F. & Avila, J. Extracellular tau is toxic to neuronal cells. FEBS Lett. 580, 4842\u20134850 (2006).","journal-title":"FEBS Lett."},{"key":"1455_CR45","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.mcn.2007.12.010","volume":"37","author":"A G\u00f3mez-Ramos","year":"2008","unstructured":"G\u00f3mez-Ramos, A., D\u00edaz-Hern\u00e1ndez, M., Rubio, A., Miras-Portugal, M. T. & Avila, J. Extracellular tau promotes intracellular calcium increase through M1 and M3 muscarinic receptors in neuronal cells. Mol. Cell. Neurosci. 37, 673\u2013681 (2008).","journal-title":"Mol. Cell. Neurosci."},{"key":"1455_CR46","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1001\/jamaneurol.2018.2505","volume":"76","author":"GS Gibbons","year":"2019","unstructured":"Gibbons, G. S., Lee, V. M. Y. & Trojanowski, J. Q. Mechanisms of cell-to-cell transmission of pathological tau: a review. JAMA Neurol. 76, 101\u2013108 (2019).","journal-title":"JAMA Neurol."},{"key":"1455_CR47","doi-asserted-by":"publisher","first-page":"667","DOI":"10.3389\/fnins.2017.00667","volume":"11","author":"K Yamada","year":"2017","unstructured":"Yamada, K. Extracellular tau and its potential role in the propagation of tau pathology. Front. Neurosci. 11, 667 (2017).","journal-title":"Front. Neurosci."},{"key":"1455_CR48","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1007\/s00401-018-1911-2","volume":"136","author":"JP Courade","year":"2018","unstructured":"Courade, J. P. et al. Epitope determines efficacy of therapeutic anti-tau antibodies in a functional assay with human Alzheimer tau. Acta Neuropathol. 136, 729\u2013745 (2018).","journal-title":"Acta Neuropathol."},{"key":"1455_CR49","doi-asserted-by":"publisher","first-page":"2635","DOI":"10.1084\/jem.20160833","volume":"213","author":"JL Guo","year":"2016","unstructured":"Guo, J. L. et al. Unique pathological tau conformers from Alzheimer\u2019s brains transmit tau pathology in nontransgenic mice. J. Exp. Med. 213, 2635\u20132654 (2016).","journal-title":"J. Exp. Med."},{"key":"1455_CR50","doi-asserted-by":"crossref","unstructured":"Czerkowicz, J. et al. Anti-tau antibody BIIB092 binds secreted tau in preclinical models and Alzheimer\u2019s disease cerebrospinal fluid. Alzheimers Dement. 14, P1441 (2018); https:\/\/alz-journals.onlinelibrary.wiley.com\/doi\/10.1016\/j.jalz.2018.06.2423","DOI":"10.1016\/j.jalz.2018.06.2423"},{"key":"1455_CR51","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.sbi.2020.05.011","volume":"64","author":"SH Scheres","year":"2020","unstructured":"Scheres, S. H., Zhang, W., Falcon, B. & Goedert, M. Cryo-EM structures of tau filaments. Curr. Opin. Struct. Biol. 64, 17\u201325 (2020).","journal-title":"Curr. Opin. Struct. Biol."},{"key":"1455_CR52","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1016\/S1474-4422(20)30489-0","volume":"20","author":"GU H\u00f6glinger","year":"2021","unstructured":"H\u00f6glinger, G. U. et al. Safety and efficacy of tilavonemab in progressive supranuclear palsy: a phase 2, randomised, placebo-controlled trial. Lancet Neurol. 20, 182\u2013192 (2021).","journal-title":"Lancet Neurol."},{"key":"1455_CR53","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31517-z","volume":"8","author":"S Hall","year":"2018","unstructured":"Hall, S. et al. Cerebrospinal fluid concentrations of inflammatory markers in Parkinson\u2019s disease and atypical parkinsonian disorders. Sci. Rep. 8, 13276 (2018).","journal-title":"Sci. Rep."},{"key":"1455_CR54","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1001\/archneurol.2012.1654","volume":"69","author":"S Hall","year":"2012","unstructured":"Hall, S. et al. 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 (2012).","journal-title":"Arch. Neurol."},{"key":"1455_CR55","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1136\/jnnp-2014-308004","volume":"86","author":"D Wagshal","year":"2015","unstructured":"Wagshal, D. et al. Divergent CSF \u03c4 alterations in two common tauopathies: Alzheimer\u2019s disease and progressive supranuclear palsy. J. Neurol. Neurosurg. Psychiatry 86, 244\u2013250 (2015).","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"1455_CR56","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1111\/nan.12208","volume":"41","author":"GG Kovacs","year":"2015","unstructured":"Kovacs, G. G. Invited review: neuropathology of tauopathies: principles and practice. Neuropathol. Appl. Neurobiol. 41, 3\u201323 (2015).","journal-title":"Neuropathol. Appl. Neurobiol."},{"key":"1455_CR57","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1080\/13543784.2018.1460356","volume":"27","author":"A Shoeibi","year":"2018","unstructured":"Shoeibi, A., Olfati, N. & Litvan, I. Preclinical, phase I, and phase II investigational clinical trials for treatment of progressive supranuclear palsy. Expert Opin. Investig. Drugs 27, 349\u2013361 (2018).","journal-title":"Expert Opin. Investig. Drugs"},{"key":"1455_CR58","doi-asserted-by":"publisher","unstructured":"Grimm, M. J. et al. Movement Disorder Society-Endorsed PSP Study Group. Clinical conditions \u2018suggestive of progressive supranuclear palsy\u2019\u2014diagnostic performance. Mov. Disord. https:\/\/doi.org\/10.1002\/mds.28263 (2020).","DOI":"10.1002\/mds.28263"},{"key":"1455_CR59","unstructured":"D\u2019Elia, L. F., Satz, P., Uchiyama, C. L. & White, T. Color Trails Test. Professional Manual (Psychological Assessment Resources, 1996)."},{"key":"1455_CR60","doi-asserted-by":"publisher","first-page":"1316","DOI":"10.1016\/j.neuroimage.2009.09.069","volume":"49","author":"R Wolz","year":"2010","unstructured":"Wolz, R., Aljabar, P., Hajnal, J. V., Hammers, A. & Rueckert, D. LEAP: learning embeddings for atlas propagation. Neuroimage 49, 1316\u20131325 (2010).","journal-title":"Neuroimage"},{"key":"1455_CR61","doi-asserted-by":"crossref","unstructured":"Guy, W. ECDEU Assessment Manual for Psychopharmacology (US Department of Health, Education, and Welfare, 1976).","DOI":"10.1037\/e591322011-001"},{"key":"1455_CR62","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1093\/arclin\/act057","volume":"28","author":"S Karantzoulis","year":"2013","unstructured":"Karantzoulis, S., Novitski, J., Gold, M. & Randolph, C. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): utility in detection and characterization of mild cognitive impairment due to Alzheimer\u2019s disease. Arch. Clin. Neuropsychol. 28, 837\u2013844 (2013).","journal-title":"Arch. Clin. Neuropsychol."},{"key":"1455_CR63","doi-asserted-by":"publisher","first-page":"47","DOI":"10.3138\/ptc.2009-08","volume":"63","author":"V Dal Bello-Haas","year":"2011","unstructured":"Dal Bello-Haas, V., Klassen, L., Sheppard, M. S. & Metcalfe, A. Psychometric properties of activity, self-efficacy, and quality-of-life measures in individuals with Parkinson disease. Physiother. Can. 63, 47\u201357 (2011).","journal-title":"Physiother. Can."},{"key":"1455_CR64","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1111\/j.2044-8260.1984.tb00626.x","volume":"23","author":"E Miller","year":"1984","unstructured":"Miller, E. Verbal fluency as a function of a measure of verbal intelligence and in relation to different types of cerebral pathology. Br. J. Clin. Psychol. 23, 53\u201357 (1984).","journal-title":"Br. J. Clin. Psychol."},{"key":"1455_CR65","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1002\/mds.26580","volume":"31","author":"M Stamelou","year":"2016","unstructured":"Stamelou, M. et al. Power calculations and placebo effect for future clinical trials in progressive supranuclear palsy. Mov. Disord. 31, 742\u2013747 (2016).","journal-title":"Mov. Disord."}],"updated-by":[{"DOI":"10.1038\/s41591-022-02076-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T00:00:00Z","timestamp":1665964800000}}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01455-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01455-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01455-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,5]],"date-time":"2023-02-05T10:08:24Z","timestamp":1675591704000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-021-01455-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["1455"],"URL":"https:\/\/doi.org\/10.1038\/s41591-021-01455-x","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8]]},"assertion":[{"value":"19 December 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 October 2022","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41591-022-02076-8","URL":"https:\/\/doi.org\/10.1038\/s41591-022-02076-8","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.L.B. reports consultancies for AGTC, Alector, Arkuda, Arvinas, Asceneuron, AZTherapies, Bioage, GSK, Humana, Lundbeck, Ono, Roche, Samumed, Sangamo, Stealth Therapeutics, Third Rock, Transposon, UCB and Wave, and research support from the Association for Frontotemporal Degeneration, Biogen, Bluefield Project to Cure Frontotemporal Dementia, Eli Lilly, Eisai, National Institutes of Health (grant nos. U19AG063911, U54NS092089 and R01AG031278) and Tau Research Consortium. L.I.G. reports consultancies for AbbVie, AlzProtect, Asceneuron, Biogen, CurePSP, Martin, Mitochon, Mitsubishi Tanabe, Pinteon, Retrotope, Roche, Stealth BioTherapeutics and UCB, and research support from AbbVie, American Parkinson\u2019s Disease Association and Biogen. G.U.H. reports consultancies for AbbVie, AlzProtect, Asceneuron, Biogen, Biohaven, Lundbeck, Novartis, Roche, Sanofi and UCB; honoraria for scientific presentations from AbbVie, Bayer Vital, Bial, Biogen, Bristol-Myers Squibb, Roche, Teva, UCB and Zambon; research collaborations with Orion, Prothena and Roche; research support from GE Health, Neuropore, German Research Foundation (DFG; EXC 2145 SyNergy, nos. 390857198, HO2402\/6-2 and HO2402\/18-1), the German Federal Ministry of Education and Research (BMBF, nos. 01KU1403A and 01EK1605A), the NOMIS foundation (FTLD project), the EU\/EFPIA\/Innovative Medicines Initiative (2) Joint Undertaking (IMPRIND, grant no. 116060) and VolkswagenStiftung\/Lower Saxony Ministry for Science\/Petermax-M\u00fcller Foundation (Nieders\u00e4chsisches Vorab). H.R.M. reports consultancies for AbbVie, Biogen, Biohaven, Denali and UCB; employment by North Thames National Institute for Health Research and University College London; lecture fees\/honoraria from Biogen, C4X Discovery, Movement Disorders Society, UCB and Wellcome Trust; research grants from CBD Solutions, Cure Parkinson\u2019s Trust, Drake Foundation, Medical Research Council, MND Association, Parkinson\u2019s UK and PSP Association; and being a coapplicant on a patent application related to C9ORF72 (method for diagnosing a neurodegenerative disease (no. PCT\/GB2012\/052140)). I.L. reports scientific advisory board membership for Corticobasal Degeneration Solutions and Lundbeck; research support from AbbVie, Biogen, Biohaven, EIP-Pharma, Roche, Lewy Body Association, Michael J. Fox Foundation, National Institutes of Health (grant nos. 5P50AG005131-33, 2R01AG038791-06A, U01NS090259, U01NS100610, U01NS80818, R25NS098999, P20GM109025, U19AG063911-1 and 1R21NS114764-01A1) and Parkinson Foundation and Parkinson Study Group; and employment at University of California San Diego and Chief Editor of <i>Frontiers in Neurology<\/i>. A.E.L. reports advisory board membership for AbbVie, AFFiRis, Biogen, Corticobasal Degeneration Solutions, Janssen, Jazz Pharma, Lilly, Lundbeck, Merck, Paladin, PhotoPharmics, Roche, Sunovion, Sun Pharma and Theravance; honoraria from AbbVie, Sunovion and Sun Pharma; grants from Brain Canada, Canadian Institutes of Health Research, Corticobasal Degeneration Solutions, Edmond J. Safra Philanthropic Foundation, Michael J. Fox Foundation, Ontario Brain Institute, the Parkinson Foundation and Parkinson Society Canada. J.-C.C. reports advisory board membership for Pfizer; consultancies for Air Liquide, AlzProtect, Biogen, Bristol-Myers Squibb, Denali and Theranexus; speaker fees from Biogen and Ever Pharma; research grants from Actelion and Michael J. Fox Foundation; and travel grants from MDS. I.A. reports consultancies for AbbVie and Biogen. M.G. reports consultancies for Biogen and Bristol-Myers Squibb. T.D., L.Y., B.T.-M., K.K., M.J.W., D.L.G., L.G., J.O. and S.B.H. are employees of, and hold stock in, Biogen. J.K. is a former employee of, and holds stock in, Biogen. K.H. reports being an independent physician pharmacovigilance professional at Biogen for the PASSPORT study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}