Faculty, Staff and Student Publications

Language

English

Publication Date

11-27-2025

Journal

npj Parkinson's Disease

DOI

10.1038/s41531-025-01215-5

PMID

41309625

PMCID

PMC12749785

PubMedCentral® Posted Date

11-27-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Mutations in LRRK2, a leading genetic cause of Parkinson's disease (PD), are linked to immune dysregulation, but the immune profiles in the periphery and central nervous system (CNS) remain incompletely defined. This study utilized a large cohort of serum samples (n = 651) and matched CSF samples (n = 129) from LRRK2 mutation carriers and non-carriers, with and without PD, to assess immune regulators using Luminex immunoassay. After correction for multiple comparisons, LRRK2 mutations were associated with significantly elevated serum levels of SDF-1 alpha and TNF-RII, while CSF markers such as BAFF, CD40L, and IL-27 were nominally reduced. Regardless of LRRK2 status, PD was associated with nominally lower levels of inflammatory analytes in CSF, with minimal changes observed in serum. Correlation analyses revealed distinct immune profiles between serum and CSF, suggesting compartmentalized immune responses. These findings highlight immune alterations in LRRK2 mutation carriers and PD, providing potential serum markers for monitoring immune responses and avenues for mechanistic studies.

Keywords

Biomarkers, Immunology, Neurology, Neuroscience

Published Open-Access

yes

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