Comparison of biospecimens for α-synuclein seed amplification assays in Parkinson's disease: A Systematic Review and Network Meta-Analysis.

Abstract

Alpha-synuclein seed amplification assays (α-syn SAAs) are promising diagnostic methods for Parkinson's disease (PD) and other synucleinopathies. However, there is limited consensus regarding the diagnostic and differential diagnostic performance of α-syn SAAs on biofluids and peripheral tissues. A comprehensive research was performed on PubMed, Web of Science, Embase, and Cochrane library. Meta-analysis was performed using a random-effects model. A Network meta-analysis (NMA) based on ANOVA model was conducted to compare the relative accuracy of α-syn SAAs on different specimens. The pooled sensitivity and specificity of α-syn SAAs distinguishing PD from HCs or NNCs were 0.91 (0.86-0.94) and 0.92 (0.87-0.95) for cerebrospinal fluid (CSF); 0.91 (0.87-0.96) and 0.93 (0.88-0.97) for skin; 0.44 (0.30-0.59) and 0.92 (0.79-0.98) for submandibular gland; 0.44 (0.30-0.59) and 0.92 (0.79-0.98) for gastrointestinal tract; 0.79 (0.70-0.86) and 0.88 (0.77-0.95) for saliva; 0.52 (0.38-0.66) and 0.91 (0.82-0.97) for olfactory mucosa (OM). The pooled sensitivity and specificity were 0.91 (0.89-0.93) and 0.50 (0.45-0.56) for CSF, 0.92 (0.83-0.97) and 0.22 (0.06-0.48) for skin, 0.61 (0.42-0.78) and 0.49 (0.33-0.65) for OM in distinguishing PD from MSA. The pooled sensitivity and specificity were 0.92 (0.89-0.94) and 0.84 (0.73-0.91) for CSF, 0.92 (0.83-0.97) and 0.88 (0.64-0.99) for skin, 0.69 (0.56-0.80) and 0.83 (0.59-0.96) for OM in distinguishing PD from PSP. The pooled sensitivity and specificity were 0.94 (0.90-0.97) and 0.95 (0.77-1.00) for CSF, 0.94 (0.84-0.99) and 0.86 (0.42-1.00) for skin in distinguishing PD from CBD. α-syn SAAs of CSF, skin, saliva, SMG and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.