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 α‐synuclein oligomers as a diagnostic biomarker for Lewy body disease. OBJECTIVE: The objective of this study was to evaluate the diagnostic performance of skin α‐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 α‐synuclein real‐time quaking‐induced conversion assay. RESULTS: Overall, the skin α‐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 α‐synuclein deposition in patients with Lewy body disease. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society