Consistency of Serial Cerebrospinal Fluid α-Synuclein Seed Amplification Assay Results in the Parkinson's Precision Medicine Initiative

BACKGROUND: Studies reporting α-synuclein seed amplification assay (aSyn-SAA) results are often cross-sectional. OBJECTIVES: In this study, we investigated the intraindividual consistency of aSyn-SAA results (Amprion) over time from participants in the Parkinson's Precision Medicine Initiative (PPMI). METHODS: A total of 1238 participants had >1 cerebrospinal fluid (CSF) aSyn-SAA result for analysis (Parkinson's disease [PD] = 633, prodromal = 563, healthy control [HC] = 42), collected over a median (minimum, maximum) of 2.0 (0.4, 11.4) years. Emphasis was placed on evaluating consistency in aSyn-SAA-PD participants, aSyn-SAA + HC participants, and conversion rates from aSyn-SAA negative to positive results prodromal participants. RESULTS: Of aSyn-SAA + PD participants, 96% (474/493, 95% confidence interval [CI]: 94%-98%) remained positive in subsequent samples, and 92% (116/126, 95% CI: 86%-96%) of aSyn-SAA-PD participants remained negative. Ninety-nine percent (303/307, 95% CI: 97%-99%) of aSyn-SAA + prodromal participants remained positive, and 95% (234/247, 95% CI: 91%-97%) of aSyn-SAA-prodromal participants remained negative. Eighty-nine percent (16/18, 95% CI: 67%-97%) of aSyn-SAA + HC participants remained positive, and 87% (20/23, 95% CI: 68%-95%) of aSyn-SAA-HC participants remained negative. CONCLUSIONS: aSyn-SAA testing is highly consistent over time, even in less expected scenarios. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.