Consistency of Serial CSF alpha-Synuclein Seed Amplification Assay Results in the Parkinson’s Progression Marker Initiative

Studies reporting alpha-synuclein seed amplification assay (aSyn-SAA) results are often cross-sectional. Here we investigated the intra-individual consistency of aSyn-SAA results over time from participants in the Parkinson's Progression Marker Initiative (PPMI). A total of 1238 participants had >1 CSF aSyn-SAA result for analysis (Parkinson's disease [PD]=633, prodromal =563, healthy control [HC]=42) which were collected over a median (min, max) of 2.0 (0.4, 11.4) years. Emphasis was placed on evaluating consistency in less common results such as aSyn-SAA- PD participants, aSyn-SAA+ HC and conversion rates from aSyn-SAA negative to positive results prodromal participants. Of aSyn-SAA+ PD participants, 96% (474/493, 95%CI 94-98%) remained positive in subsequent samples, and 92% (116/126, 95%CI 86-96%) of aSyn-SAA- PD participants remained negative. 99% (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. 89% (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. These results confirm a high consistency of aSyn-SAA results over time, even in less expected results.