RT-QuIC Detection of Pathological α-Synuclein in Skin Punches of Patients with Lewy Body Disease

Background Evidence suggests that skin represents a suitable matrix for demonstrating alpha-synuclein oligomers as a diagnostic biomarker for Lewy body disease. Objective The objective of this study was to evaluate the diagnostic performance of skin alpha-syn real-time quaking-induced conversion assay in patients with Lewy body disease. Methods We analyzed skin punches taken in vitam (n = 69) or postmortem (n = 49) from patients with PD, dementia with Lew bodies (DLB), incidental Lewy body pathology, and neurological controls. Seventy-nine patients underwent both CSF and skin alpha-synuclein real-time quaking-induced conversion assay. Results Overall, the skin alpha-synuclein real-time quaking-induced conversion assay distinguished Lewy body disease patients with 94.1% accuracy (sensitivity, 89.2%; specificity, 96.3%). Assay sensitivity reached 94.1% in the 17 Lewy body disease patients analyzed in the cervical region. In patients with both CSF and skin samples, the 2 real-time quaking-induced conversion assay protocols yielded similar diagnostic accuracy (skin, 97.5%; CSF, 98.7%). Conclusion Skin punch biopsies might represent a valid and convenient alternative to CSF analysis to demonstrate Lew body-related alpha-synuclein deposition in patients with Lewy body disease. (c) 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society