Diagnostic value of α-synuclein seeding amplification assays in α-synucleinopathies: A systematic review and meta-analysis

Alpha-synuclein(αSyn) aggregates are definite pathological hallmarks of α-synucleinopathies. Seeding amplification assays (SAAs) have been developed to detect trace amounts of αSyn oligomers in vivo.. Herein, we assessed the diagnostic accuracy of the αSyn-SAAs across biospecimens, diagnostic references, methods, and subtypes. A systematic literature search yielded 36 eligible studies for a meta-analysis of the sensitivity and specificity of αSyn-SAAs in patients with α-synucleinopathies(n = 2722) and controls(n = 2278). Pooled sensitivities and specificities with 95% confidence intervals (CIs) were calculated using bivariate random-effects models and a meta-regression analysis was performed. The summary sensitivity and specificity of αSyn-SAAs positivity for the diagnosis of α-synucleinopathies were 0.88(95% CIs = 0.84–0.91) and 0.95(0.93–0.97), respectively. Two covariates (biospecimen and diagnostic reference) were significant in fitting the meta-regression model (likelihood-ratio test for sensitivity and specificity, p