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Lookup NU author(s): Dr Jacopo Pasquini, Professor Nicola PaveseORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.Background: The cerebrospinal fluid alpha-synuclein seed amplification assay (CSFasynSAA) detects alpha-synuclein aggregation in over 90% of individuals with sporadic PD (sPD). However, the clinical characteristics of sPD with negative CSFasynSAA remain undefined. Objectives: Describe clinical and neuroimaging characteristics of CSFasynSAA-negative sPD individuals in the Parkinson's Progression Markers Initiative (PPMI). Methods: We identified sPD PPMI participants with a negative CSFasynSAA (SAA−, n = 80) or positive CSFasynSAA (SAA+, n = 856) result at baseline. For comparative analysis between groups, we used a reduced dataset (n = 79 SAA− and n = 237 SAA+) propensity-score matched on age, sex, and time since clinical diagnosis. Clinical parameters, dopamine transporter-single photon emission computed tomography (DAT-SPECT), and magnetic resonance imaging (MRI) brain volumetrics were analyzed. Results: The SAA− and matched SAA+ groups had similar motor performance on the Movement Disorder Society Unified Parkinson's Disease Rating Scale-Part III (MDS-UPDRS-III) and similar cognitive performance on the Montreal Cognitive Assessment (MoCA) at baseline. The proportion with severe hyposmia was 12% for SAA− versus 73% for SAA+ (P < 0.001). Per PPMI enrollment criteria all participants were classified as having an abnormal DAT-SPECT. There were no significant differences in median quantitative DAT-SPECT measures between groups. The SAA− group showed a higher degree of atrophy in subcortical brain regions including substantia nigra. Longitudinally, 14.3% of SAA− participants had a change in diagnosis versus 0.9% of SAA+ participants. Conclusions: At baseline, SAA− 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− participants have a greater degree of subcortical brain atrophy, and approximately one out of seven SAA− participants received a change in diagnosis. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Author(s): Brooker SM, Pasquini J, Choi SH, Lafontant D-E, Fereshtehnejad S-M, Zeighami Y, Grillo P, Riboldi GM, Azizi H, Moqadam R, Kang UJ, Nudelman KNH, Siderowf A, Tanner CM, Tropea TF, Foroud T, Chahine LM, Mollenhauer B, Merchant KM, Galasko D, Coffey CS, Dobkin RD, Brown EG, Alcalay RN, Weintraub D, Marek K, Simuni T, Gonzalez-Latapi P, Pavese N, Poston KL
Publication type: Article
Publication status: Published
Journal: Movement Disorders
Year: 2026
Pages: epub ahead of print
Online publication date: 28/01/2026
Acceptance date: 05/01/2026
Date deposited: 02/03/2026
ISSN (print): 0885-3185
ISSN (electronic): 1531-8257
Publisher: John Wiley and Sons Inc
URL: https://doi.org/10.1002/mds.70197
DOI: 10.1002/mds.70197
Data Access Statement: The data that support the findings of this study are openly available in PPMI database at http://www.ppmiinfo.org/access-data-specimens/download-data, reference number RRID:SCR_006431.
PubMed id: 41603617
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