Objective: We performed meta-analysis to determine the diagnostic and differential diagnostic value of α-syn SAAs for PD, and to investigate the optimal specimens.

Background: 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.

Method: A comprehensive research was performed on PubMed, Web of Science, Embase, and Cochrane library from 2016 to 1 December 2022. Meta-analysis was performed using a random-effects model. The pooled estimates with 95% confidence interval of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR), with summary receiver operating characteristic (SROC) curves were used to determine the diagnostic performance. A Network meta-analysis (NMA) based on ANOVA model was conducted to compare the relative accuracy of α-syn SAAs on different specimens.

Results: The pooled sensitivity and specificity of α-syn SAAs distinguishing PD from HCs or NNCs were ​0.91 (0.90-0.93) and 0.95 (0.93-0.96) for cerebrospinal fluid (CSF); 0.92 (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 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). NMA indicated CSF SAAs had the highest relative sensitivity, specificity and DOR, followed by skin sample. The pooled sensitivity and specificity of α-syn SAAs distinguishing PD from MSA 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. The pooled sensitivity and specificity of α-syn SAAs distinguishing PD from PSP 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. The pooled sensitivity, specificity of α-syn SAAs distinguishing PD from CBD 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.

Conclusion: α-syn SAAs of CSF, skin, saliva and OM are promising diagnostic assays for PD, with CSF and skin α-syn SAAs demonstrating higher diagnostic performance.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/comparison-of-biospecimens-for-%ce%b1-synuclein-seed-amplification-assays-in-parkinsons-disease-a-systematic-review-and-network-meta-analysis/