Alison J E Green

Background The neuropathology of Parkinson's disease (PD) associated with leucine‐rich repeat kinase 2 (LRRK2) mutations (LRRK2‐PD) is heterogeneous and varies with the type of mutation. There are only a few studies evaluating seeding aggregation assays to detect α‐synuclein (α‐syn) in patients with LRRK2‐PD. Objective We aimed to investigate whether α‐syn real‐time quaking induced conversion (RT‐QuIC) is a sensitive biomarker of synucleinopathy in LRRK2‐PD. Methods We studied α‐syn RT‐QuIC in brain tissue and postmortem ventricular cerebrospinal fluid (CSF) of LRRK2‐PD cases with and without Lewy‐type pathology. Results The accuracy of α‐syn RT‐QuIC in substantia nigra and CSF samples of patients with LRRK2‐PD was 100%. The test also obtained 100% sensitivity to detect misfolded α‐syn in substantia nigra of cases with idiopathic PD and was negative in the substantia nigra of all the control brains without Lewy‐type pathology. Conclusions Substantia nigra and ventricular CSF RT‐QuIC discriminates with high sensitivity and specificity LRRK2 cases with Lewy‐type pathology from those without it. RT‐QuIC assay could be of particular interest in the selection of cases for clinical trials in this genetic form of PD. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.