CSF alpha-synuclein seed amplification assay shows high intra-individual consistency in Parkinson's disease

This observational review analyzed data from 1238 participants in the Parkinson's Progression Marker Initiative (PPMI), including individuals with Parkinson's disease, prodromal Parkinson's disease, and healthy controls. The study assessed the intra-individual consistency of serial cerebrospinal fluid alpha-synuclein seed amplification assay (aSyn-SAA) results over a median follow-up of 2.0 years (range 0.4 to 11.4 years). The primary outcome was the stability of aSyn-SAA status (positive or negative) in subsequent samples.

Results showed high consistency across groups. Among participants with Parkinson's disease, 96% (474/493) who were initially aSyn-SAA positive remained positive (95% CI 94-98%), and 92% (116/126) who were initially negative remained negative (95% CI 86-96%). In prodromal participants, 99% (303/307) of initially positive individuals remained positive (95% CI 97-99%), and 95% (234/247) of initially negative individuals remained negative (95% CI 91-97%). Healthy controls showed slightly lower consistency, with 89% (16/18) of positive and 87% (20/23) of negative results remaining stable.

Safety and tolerability data for the serial lumbar punctures were not reported. Key limitations include the observational design, which cannot establish causality, and the lack of reported funding or conflicts of interest. The practice relevance was not reported. The findings demonstrate the assay's technical reliability for longitudinal research in defined cohorts but do not establish its role in routine clinical diagnosis or monitoring.