α-Synuclein Seed Amplification Assay Amplification Parameters and the Risk of Progression in Prodromal Parkinson Disease
David G. Coughlin, Ben Shifflett, Carly M. Farris, Yihua Ma, Douglas Galasko, Steven D. Edland, Brit Mollenhauer, Michael C. Brumm, Kathleen L. Poston, Kenneth Marek, Andrew Siderowf, Claudio Soto, Luis Concha‐Marambio, as the Investigators of the Parkinson's Progression Marker Initiative
Abstract
OBJECTIVES: 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 (αSyn-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. METHODS: Cross-sectional and longitudinal CSF αSyn-SAA results from participants in the Parkinson's Progression Markers Initiative were analyzed. αSyn-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. RESULTS: < 0.0001). There were no changes in 48 participants with prodromal PD with longitudinal assays. DISCUSSION: αSyn-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.