{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:04:54Z","timestamp":1789549494384,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T00:00:00Z","timestamp":1769558400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["K08NS138592"],"award-info":[{"award-number":["K08NS138592"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n The cerebrospinal fluid alpha\u2010synuclein seed amplification assay (CSFasynSAA) detects alpha\u2010synuclein aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA remain undefined.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n Describe clinical and neuroimaging characteristics of CSFasynSAA\u2010negative sPD individuals in the Parkinson's Progression Markers Initiative (PPMI).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We identified sPD PPMI participants with a negative CSFasynSAA (SAA\u2212, n\u2009=\u200980) or positive CSFasynSAA (SAA+, n\u2009=\u2009856) result at baseline. For comparative analysis between groups, we used a reduced dataset (n\u2009=\u200979 SAA\u2212 and n\u2009=\u2009237 SAA+) propensity\u2010score matched on age, sex, and time since clinical diagnosis. Clinical parameters, dopamine transporter\u2010single photon emission computed tomography (DAT\u2010SPECT), and magnetic resonance imaging (MRI) brain volumetrics were analyzed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The SAA\u2212 and matched SAA+ groups had similar motor performance on the Movement Disorder Society Unified Parkinson's Disease Rating Scale\u2010Part III (MDS\u2010UPDRS\u2010III) and similar cognitive performance on the Montreal Cognitive Assessment (MoCA) at baseline. The proportion with severe hyposmia was 12% for SAA\u2212 versus 73% for SAA+ (\n P<\/jats:italic>\n \u2009<\u20090.001). Per PPMI enrollment criteria all participants were classified as having an abnormal DAT\u2010SPECT. There were no significant differences in median quantitative DAT\u2010SPECT measures between groups. The SAA\u2212 group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, 14.3% of SAA\u2212 participants had a change in diagnosis versus 0.9% of SAA+ participants.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n At baseline, SAA\u2212 sPD PPMI participants have a substantially lower rate of hyposmia, but otherwise cannot be readily distinguished from SAA+ participants based on clinical characteristics. However, SAA\u2212 participants have a greater degree of subcortical brain atrophy, and approximately one out of seven SAA\u2212 participants received a change in diagnosis. \u00a9 2026 The Author(s).\n Movement Disorders<\/jats:italic>\n published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mds.70197","type":"journal-article","created":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T13:58:16Z","timestamp":1769608696000},"page":"1114-1127","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha\u2010Synuclein Seed Amplification Assay"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5674-3124","authenticated-orcid":false,"given":"Sarah M.","family":"Brooker","sequence":"first","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacopo","family":"Pasquini","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University Newcastle upon Tyne UK"},{"name":"Department of Clinical and Experimental Medicine University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5257-5741","authenticated-orcid":false,"given":"Seung Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David\u2010Erick","family":"Lafontant","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, College of Public Health University of Iowa Iowa City Iowa USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-9351","authenticated-orcid":false,"given":"Seyed\u2010Mohammad","family":"Fereshtehnejad","sequence":"additional","affiliation":[{"name":"Division of Neurology Toronto Western Hospital, University of Toronto Toronto Ontario Canada"},{"name":"Edmond J. Safra Program in Parkinson's Disease and the Morton and Gloria Shulman Movement Disorders Clinic Toronto Western Hospital, UHN Toronto Ontario Canada"},{"name":"Department of Neurobiology, Care Sciences and Society (NVS) Karolinska Institute Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yashar","family":"Zeighami","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University Montreal Quebec Canada"},{"name":"Integrated Program in Neuroscience McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Grillo","sequence":"additional","affiliation":[{"name":"The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders Department of Neurology, NYU Langone Health New York New York USA"},{"name":"Department of Brain and Behavioral Sciences University of Pavia Pavia Italy"},{"name":"IRCCS Mondino Foundation Pavia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulietta M.","family":"Riboldi","sequence":"additional","affiliation":[{"name":"Department of Neurology NYU Grossman School of Medicine New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houman","family":"Azizi","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University Montreal Quebec Canada"},{"name":"Integrated Program in Neuroscience McGill University Montreal Quebec Canada"},{"name":"Neuro (Montreal Neurological Institute\u2010Hospital) McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roqaie","family":"Moqadam","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Department of Psychiatry McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5970-6839","authenticated-orcid":false,"given":"Un Jung","family":"Kang","sequence":"additional","affiliation":[{"name":"The Marlene and Paolo Fresco Institute for Parkinson's and Movement Disorders Department of Neurology, NYU Langone Health New York New York USA"},{"name":"Department of Neurology NYU Grossman School of Medicine New York New York USA"},{"name":"Department of Neuroscience NYU Grossman School of Medicine New York New York USA"},{"name":"Parekh Center for interdisciplinary Neurology NYU Langone Health New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly N.H.","family":"Nudelman","sequence":"additional","affiliation":[{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis Indiana 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University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lana M.","family":"Chahine","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pittsburgh Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brit","family":"Mollenhauer","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center G\u00f6ttingen G\u00f6ttingen Germany"},{"name":"Paracelsus\u2010Elena\u2010Klinik Kassel Kassel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana M.","family":"Merchant","sequence":"additional","affiliation":[{"name":"Department of Neurology Northwestern University Feinberg School of Medicine Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Galasko","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of 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N.","family":"Alcalay","sequence":"additional","affiliation":[{"name":"Division of Movement Disorders, Department of Neurology Tel Aviv Soursaky Medical Center Tel Aviv Israel"},{"name":"Columbia University Irving Medical Center New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0633-7168","authenticated-orcid":false,"given":"Daniel","family":"Weintraub","sequence":"additional","affiliation":[{"name":"Department of Neurology University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry University of Pennsylvania School of Medicine Philadelphia Pennsylvania USA"},{"name":"Philadelphia Department of Veterans Affairs Parkinson's Disease Research, Education and Clinical Center Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth","family":"Marek","sequence":"additional","affiliation":[{"name":"Institute for Neurodegenerative Disorders New Haven 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