Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha-Synuclein Seed Amplification Assay.
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Brooker Sarah M, Pasquini Jacopo, Choi Seung Ho, Lafontant David-Erick, Fereshtehnejad Seyed-Mohammad, Zeighami Yashar, Grillo Piergiorgio, Riboldi Giulietta M, Azizi Houman, Moqadam Roqaie, Kang Un Jung, Nudelman Kelly N H, Siderowf Andrew, Tanner Caroline M, Tropea Thomas F, Foroud Tatiana, Chahine Lana M, Mollenhauer Brit, Merchant Kalpana M, Galasko Douglas, Coffey Christopher S, Dobkin Roseanne D, Brown Ethan G, Alcalay Roy N, Weintraub Daniel, Marek Kenneth, Simuni Tanya, Gonzalez-Latapi Paulina, Pavese Nicola, Poston Kathleen L, Parkinson's Progression Markers Initiative
Аннотация
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.