AbstractBackgroundAggregation of α‐synuclein (oligomeric α‐syn) has been considered as the pathological hallmark of Parkinson's disease (PD) and multiple system atrophy (MSA). Studies showed oligomeric α‐syn/total α‐syn ratio was increased in the saliva of patients with PD, suggesting that seeding activity of salivary oligomeric α‐syn may be a novel biomarker for the diagnosis of PD and MSA.ObjectiveThis study aimed to evaluate the diagnostic value of salivary α‐syn seeding activity in patients with PD and MSA.MethodsA total of 75 patients with PD, 18 patients with MSA, and 36 nonneurodegenerative healthy control subjects underwent salivary α‐syn real‐time quaking‐induced conversion (RT‐QuIC) assay.ResultsSalivary α‐syn RT‐QuIC assay distinguished patients with PD with 76.0% sensitivity (95% confidence interval [CI], 66.1–85.9) and 94.4% specificity (95% CI, 86.6–100.0). RT‐QuIC assay sensitivity reached 61.1% (95% CI, 36.2–86.1) in patients with MSA. No significant differences were observed in the diameter of salivary α‐syn fibrils examined by electron microscopy and in thioflavin T fluorescence intensity of salivary α‐syn fibrils detected by RT‐QuIC assay between patients with PD and MSA. Notably, the lag phase of RT‐QuIC assay from patients with PD was significantly shorter than that of patients with MSA, which might be clinically applicable to the discrimination between PD and MSA.ConclusionsSalivary α‐syn seeding activity may serve as a novel biomarker for the clinical diagnosis of PD and MSA.© 2022 International Parkinson and Movement Disorder Society © 2022 International Parkinson and Movement Disorder Society