Evaluating the Role of α-Synuclein Seed Amplification as a Disease Progression Marker: Evidence and Uncertainties

Abstract

Background: α-synuclein seeding amplification assay (α-synuclein SAA) development as a diagnostic biomarker for Parkinson's disease (PD) has shown promising results over the past decade. However, the utility of these assays in the prediction of disease progression is unclear. Objectives: To assess the relationship between α-synuclein SAA and PD-specific clinical outcome measures. Methods: We extracted longitudinal data on individuals with sporadic PD from the Parkinson's Progression Markers Initiative at baseline and 5 years follow-up. Primary outcome measures included MDS-UPDRS Part III, Montreal Cognitive Assessment (MoCA) and L-dopa equivalent daily dose (LEDD). Secondary outcome measures included REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) question-6 and other non-motor assessments. α-synuclein SAA kinetic parameters were added to linear regression models to assess their impact on model fit. Results: We included 279 participants in the final analysis. There was no consistent evidence that α-synuclein SAA parameters at baseline improved our prediction models for MDS-UPDRS Part III, MoCA or LEDD at 5 years. α-synuclein SAA kinetic parameters improved model fit for RBDSQ question-6 and indicated that fast seeding profiles were associated with higher scores. Conclusions: We did not find evidence of a relationship between α-synuclein SAA and disease progression however α-synuclein SAA was associated with RBDSQ. Further work is needed to understand the factors influencing α-synuclein aggregation kinetics and the role of α-synuclein SAA in disease prognosis.