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

Autor: Alicia Garrido, Graham Fairfoul, Eduardo Tolosa, Maria J. Marti, Mario Ezquerra, Alison J E Green
Rok vydání: 2022
Předmět:
Zdroj: Garrido, A, Fairfoul, G, Tolosa, E, Marti, M J, Ezquerra, M & Green, A J E 2022, ' Brain and Cerebrospinal Fluid α-Synuclein Real-Time Quaking-Induced Conversion Identifies Lewy Body Pathology in LRRK2-PD ', Movement Disorders . https://doi.org/10.1002/mds.29284
ISSN: 1531-8257
DOI: 10.1002/mds.29284
Popis: 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.
Databáze: OpenAIRE
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