Alpha‐synuclein quantitative seed amplification assay predicts conversion to dementia

INTRODUCTION: The alpha-synuclein seed amplification assay (SAA) has shown excellent performance in the detection of Lewy body pathology in cerebrospinal fluid (CSF). Lewy body pathology is prognostically relevant in patients at risk for dementia. Current assays only provide binary results, so there is a need to quantify the extent of pathology in living patients. METHODS: In addition to the "standard" SAA, we developed a quantitative SAA (qnSAA) and measured 432 CSF samples (216 baseline-follow-up pairs). RESULTS: qnSAA results correlated with cognitive performance. Seventy-five percent of participants with fast qnSAA kinetics converted to dementia in the observed interval. Overall, participants with fast qnSAA kinetics accounted for 27.3% of dementia converters in the entire cohort. DISCUSSION: Findings demonstrate promising properties of qnSAA measurements in a cohort of patients at risk for dementia. qnSAA results showed improved prognostic relevance and have potential to measure target engagement of therapies against Lewy body pathology.