Prediction of α-Synuclein Seed Amplification Assay Positivity in Remotely Followed LRRK2 G2019S Carriers Using a Validated Data-Driven Model

The α-synuclein seed amplification assay (SAA) is a biomarker for Parkinson's disease (PD) but requires cerebrospinal fluid.We applied a validated model to predict α-synuclein SAA+ using remotely collected data in LRRK2 G2019S carriers.VALOR-PD participants completed at-home olfactory and autonomic assessments.SAA+ probabilities for manifest and non-manifest carriers at baseline and month 36 visits were estimated.Baseline SAA+ mean probability was 0.57 (manifest) and 0.28 (non-manifest).Over three years, SAA+ mean probabilities increased in manifest (0.66, p=0.014) and non-manifest carriers (0.38, p<0.001), paralleling olfactory declines.Remotely collected data may be used to approximate SAA classification.