Prediction of α-synuclein seed amplification assay positivity in remotely followed LRRK2 G2019S carriers using a validated data-driven model.

Abstract

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.