Mutations in GBA and LRRK2 Are Not Associated with Increased Inflammatory Markers

Avner Thaler*, Nurit Omer, Nir Giladi, Tanya Gurevich, Anat Bar-Shira, Mali Gana-Weisz, Orly Goldstein, Meir Kestenbaum, Julia C. Shirvan, Jesse M. Cedarbaum, Avi Orr-Urtreger, Keren Regev, Shani Shenhar-Tsarfaty, Anat Mirelman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1285-1296
Number of pages12
JournalJournal of Parkinson's Disease
Volume11
Issue number3
DOIs
StatePublished - 2021

Funding

FundersFunder number
Israeli Innovation Authority
LTI
Medison
Phonet-ica Ltd.
Sagol School of Neuroscience and Parkinson’s Foundation
Serono
Michael J. Fox Foundation for Parkinson's Research
National Parkinson Foundation
Bristol-Myers Squibb
Pfizer
Novartis
Roche
Biogen
Teva Pharmaceutical Industries
Seventh Framework Programme
Sanofi Genzyme
Israel Science Foundation

    Keywords

    • GBA
    • LRRK2
    • Parkinson's disease
    • inflammation

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