1. Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers
- Author
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Mali Gana-Weisz, Meir Kestenbaum, Julia C Shirvan, Shani Shenhar-Tsarfaty, Tanya Gurevich, Avi Orr-Urtreger, Anat Bar-Shira, Avner Thaler, Nurit Omer, Orly Goldstein, Keren Regev, Jesse M. Cedarbaum, Nir Giladi, and Anat Mirelman
- Subjects
0301 basic medicine ,Research Report ,Parkinson's disease ,Inflammation ,Disease ,medicine.disease_cause ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Immune system ,medicine ,Humans ,Mutation ,business.industry ,Neurodegeneration ,LRRK2 ,Parkinson Disease ,medicine.disease ,Ashkenazi jews ,nervous system diseases ,030104 developmental biology ,Immunology ,Parkinson’s disease ,Cytokines ,Glucosylceramidase ,GBA ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Biomarkers - Abstract
Background: Inflammation is an integral part of neurodegeneration including in Parkinson’s disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated. Objective: To assess central and peripheral cytokines among PD patients with mutations in the LRRK2 and GBA genes and among non-manifesting carriers (NMC) of these mutations in order to determine the role of inflammation in genetic PD. Methods: The following cytokines were assessed from peripheral blood and cerebrospinal fluid (CSF): TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10 and INF- γ. A comprehensive intake including general medical conditions, use of anti-inflammatory treatments, motor and cognitive assessments and additional laboratory measures were recorded, enabling the construction of the MDS probable prodromal score. Results: Data from 362 participants was collected: 31 idiopathic PD (iPD), 30 LRRK2-PD, 77 GBA-PD, 3 homozygote GBA-PD, 3 GBA-LRRK2-PD, 67 LRRK2-NMC, 105 GBA-NMC, 14 LRRK2-GBA-NMC, and 32 healthy controls. No between-group differences in peripheral or CSF cytokines were detected. No correlation between disease characteristics or risk for prodromal PD could be associated with any inflammatory measure. Conclusion: In this study, we could not detect any evidence on dysregulated immune response among GBA and LRRK2 PD patients and non-manifesting mutation carriers.
- Published
- 2021