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

Automated summary

Skin alpha-synuclein real-time quaking-induced conversion assay can accurately distinguish patients with Lewy body disease. Furthermore, the two real-time quaking-induced conversion assay protocols showed similar diagnostic accuracy when analyzing both CSF and skin samples from patients.