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: 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 αSyn-SAA+ participants with prodromal PD and PD than αSyn-SAA+ NMCs and HC participants (Kruskal-Wallis χ 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.