ALPHA-SYNUCLEIN DETECTION IN SKIN SAMPLES BY SEED AMPLIFICATION ASSAY FOR PARKINSON’S DISEASE DIAGNOSIS IN CHILEAN PATIENTS

Background: The pathological accumulation of α-synuclein (α-syn) aggregates is a hallmark biomarker of Parkinson’s disease (PD). Seed amplification assays (SAAs) offer a highly sensitive approach for detecting these aggregates, enabling early and minimally invasive diagnosis.
Methods: We aimed to assess the diagnostic accuracy, reliability, and reproducibility of SAAs, as well as to explore their correlation with clinical markers of PD. Skin punch biopsies (3 mm diameter; 14 PD, 17 healthy controls) from Chilean participants were analyzed. Each sample was tested in quadruplicate, and a sample was considered positive when at least three out of four replicates crossed the background fluorescence threshold.
Results: SAA reactions seeded with PD samples produced fibrillary α-syn aggregates, whereas control samples did not induce conversion of the recombinant α-syn substrate. The lag phase was significantly shorter in PD samples compared to controls (p < 0.01), indicating faster seeding kinetics in the disease state. No correlation was found between clinical measures and seeding activity.
Conclusions: This study is the first to evaluate SAA technology for PD diagnosis in a Chilean cohort. Our findings validate the feasibility of detecting pathological α-syn from minimally invasive samples using SAA, supporting its potential for early diagnosis. Further studies are needed to refine assay conditions and validate the clinical utility of SAAs as a non-invasive, cost-effective diagnostic tool.