a-Synuclein Seed Amplification Assay Amplification Parameters and the Risk of Progression in Prodromal Parkinson Disease.

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Abstract

Tools are needed to evaluate the risk of developing Parkinson disease (PD) in at-risk populations. In this study, we examine differences in alpha-synuclein seed amplification assay (aSyn-SAA) qualitative results and amplification parameters between nonmanifesting carriers (NMCs) of PD-related pathogenic variants, prodromal PD, and PD and the risk of developing a synucleinopathy in participants with prodromal PD.Cross-sectional and longitudinal CSF aSyn-SAA results from participants in the Parkinson's Progression Markers Initiative were analyzed. aSyn-SAA positivity and amplification parameters (maximum fluorescence [Fmax], time-to-threshold [TTT], time-to-50% Fmax [T50], and area under the curve [AUC]) were compared between NMCs, participants with prodromal PD, and participants with PD, and their relationship with the likelihood of phenoconversion in participants with prodromal PD was investigated.Samples from 1,027 participants were analyzed (159 healthy controls [HCs], 247 NMCs, 96 participants with prodromal PD, and 525 participants with PD). TTT and T50 were faster, and AUC was higher in aSyn-SAA+ participants with prodromal PD and PD than aSyn-SAA+ NMCs and HC participants (Kruskal-Wallis ?2 = 4.15-13.96, p < 0.0002-0.04). Participants with prodromal PD with positive aSyn-SAA tests and faster TTT had higher rates of phenoconversion (log-rank p = 0.001 and log-rank test-for-trend p < 0.0001). There were no changes in 48 participants with prodromal PD with longitudinal assays.aSyn-SAA positivity and faster seed amplification are associated with a greater risk of developing PD in at-risk individuals and may aid in predicting phenoconversion.

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