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

J Parkinsons Dis. 2021;11(3):1285-1296. doi: 10.3233/JPD-212624.

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.

Keywords: GBA; LRRK2; Parkinson’s disease; inflammation.

MeSH terms

  • Biomarkers / analysis
  • Cytokines / analysis
  • Glucosylceramidase* / genetics
  • Humans
  • Inflammation* / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2* / genetics
  • Mutation / genetics
  • Parkinson Disease* / genetics
  • Parkinson Disease* / pathology

Substances

  • Biomarkers
  • Cytokines
  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
  • Glucosylceramidase