Journal article
Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha-Synuclein Seed Amplification Assay
Movement disorders, PMID 8610688
01/28/2026
DOI: 10.1002/mds.70197
PMID: 41603617
Abstract
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.
Describe clinical and neuroimaging characteristics of CSFasynSAA-negative sPD individuals in the Parkinson's Progression Markers Initiative (PPMI).
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.
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.
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.
Details
- Title: Subtitle
- Clinical and Imaging Characteristics of Parkinson's Disease with Negative Alpha-Synuclein Seed Amplification Assay
- Creators
- Sarah M Brooker - Northwestern UniversityJacopo Pasquini - University of PisaSeung Ho Choi - University of IowaDavid-Erick Lafontant - University of IowaSeyed-Mohammad Fereshtehnejad - Karolinska InstitutetYashar Zeighami - Douglas Mental Health University InstitutePiergiorgio Grillo - University of PaviaGiulietta M Riboldi - New York UniversityHouman Azizi - Montreal Neurological Institute and HospitalRoqaie Moqadam - Douglas Mental Health University InstituteUn Jung Kang - NYU Langone HealthKelly N H Nudelman - Indiana University School of MedicineAndrew Siderowf - University of PennsylvaniaCaroline M Tanner - University of California, San FranciscoThomas F Tropea - Institute for Neurodegenerative DisordersTatiana Foroud - Indiana University School of MedicineLana M Chahine - University of PittsburghBrit Mollenhauer - Paracelsus Elena Klinik KasselKalpana M Merchant - Northwestern UniversityDouglas Galasko - University of California San DiegoChristopher S Coffey - University of IowaRoseanne D Dobkin - Rutgers, The State University of New JerseyEthan G Brown - University of California, San FranciscoRoy N Alcalay - Columbia University Irving Medical CenterDaniel Weintraub - University of PennsylvaniaKenneth Marek - Institute for Neurodegenerative DisordersTanya Simuni - Northwestern UniversityPaulina Gonzalez-Latapi - Northwestern UniversityNicola Pavese - Newcastle UniversityKathleen L Poston - Stanford UniversityParkinson's Progression Markers Initiative
- Resource Type
- Journal article
- Publication Details
- Movement disorders, PMID 8610688
- DOI
- 10.1002/mds.70197
- PMID
- 41603617
- ISSN
- 1531-8257
- eISSN
- 1531-8257
- Publisher
- Wiley
- Grant note
- Michael J. Fox Foundation for Parkinson's Research K08NS138592 / NINDS NIH HHS
- Language
- English
- Electronic publication date
- 01/28/2026
- Academic Unit
- Biostatistics
- Record Identifier
- 9985132205002771
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