Brain and Cerebrospinal Fluid a-Synuclein Real-Time Quaking-Induced Conversion Identifies Lewy Body Pathology in LRRK2-PD

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 alpha-synuclein (alpha-syn) in patients with LRRK2-PD. Objective: We aimed to investigate whether alpha-syn real-time quaking induced conversion (RT-QuIC) is a sensitive biomarker of synucleinopathy in LRRK2-PD.MethodsWe studied alpha-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 alpha-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 alpha-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. (C) 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Automated summary

The real-time quaking induced conversion (RT-QuIC) assay has been found to be a sensitive biomarker for synucleinopathy in patients with LRRK2-associated Parkinson's disease (LRRK2-PD). The study showed that the RT-QuIC assay had 100% accuracy and sensitivity in detecting misfolded alpha-synuclein in the substantia nigra and cerebrospinal fluid samples of LRRK2-PD patients, and it could effectively differentiate LRRK2-PD cases with Lewy-type pathology from those without it.