Dermal Real‐Time Quaking‐Induced Conversion Is a Sensitive Marker to Confirm Isolated Rapid Eye Movement Sleep Behavior Disorder as an Early α‐Synucleinopathy

Background Skin biopsy is a potential tool for the premortem confirmation of an α‐synucleinopathy. Objective The aim was to assess the aggregation assay real‐time quaking‐induced conversion (RT‐QuIC) of skin biopsy lysates to confirm isolated rapid eye movement sleep behavior disorder (iRBD) as an α‐synucleinopathy. Methods Skin biopsies of patients with iRBD, Parkinson's disease (PD), and controls were analyzed using RT‐QuIC and immunohistochemical detection of phospho‐α‐synuclein. Results α‐Synuclein aggregation was detected in 97.4% of iRBD patients (78.4% of iRBD biopsies), 87.2% of PD patients (70% of PD biopsies), and 13% of controls (7.9% of control biopsies), with a higher seeding activity in iRBD compared to PD. RT‐QuIC was more sensitive but less specific than immunohistochemistry. Conclusions Dermal RT‐QuIC is a sensitive method to detect α‐synuclein aggregation in iRBD, and high seeding activity may indicate a strong involvement of dermal nerve fibers in these patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.