Value of in vivo α‐synuclein deposits in Parkinson's disease: A systematic review and meta‐analysis

: Previous studies that have investigated the potential of in vivo abnormal α-synuclein deposits as a pathological biomarker for PD included few participants and reported different diagnostic accuracies. Here, we aimed to confirm the diagnostic value of in vivo α-synuclein deposits in PD through a systematic review and meta-analysis, with special emphasis on determining the tissue most suitable for examination and assessing whether anti-native α-synuclein or anti-phosphorylated α-synuclein antibodies should be used. Databases were searched on December 30, 2018. We finally included 41 case-control studies that examined in vivo tissue samples using anti-native α-synuclein or anti-phosphorylated α-synuclein antibody in PD patients and controls. Using a univariate random-effects model, pooled sensitivity and specificity (95% confidence interval) of anti-native α-synuclein antibody were 0.54 (0.49-0.60) and 0.72 (0.68-0.76) for the gastrointestinal tract and 0.76 (0.60-0.89) and 0.60 (0.43-0.74) for the skin. Pooled sensitivity and specificity (95% confidence interval) of anti-phosphorylated α-synuclein antibody were 0.43 (0.37-0.48) and 0.82 (0.78-0.86) for the gastrointestinal tract, 0.76 (0.69-0.82) and 1.00 (0.98-1.00) for the skin, 0.42 (0.26-0.59) and 0.94 (0.84-0.99) for the minor salivary glands, and 0.66 (0.51-0.79) and 0.96 (0.86-1.00) for the submandibular glands. Although ubiquitous heterogeneity between the included studies should be noted when interpreting our results, our analyses demonstrated the following: (1) in vivo α-synuclein immunoreactivity has the potential as a pathological biomarker for PD; (2) anti-phosphorylated α-synuclein antibody consistently has higher specificity than anti-native α-synuclein antibody; and (3) skin biopsy examination using anti-phosphorylated α-synuclein antibody has the best diagnostic accuracy, although feasibility remains an important issue. © 2019 International Parkinson and Movement Disorder Society.