Soluble immune factor profiles in blood and CSF associated with LRRK2 mutations and Parkinson’s disease
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.
Authors
- Hussein A. Tawbi (ORCID: https://orcid.org/0000-0003-1942-851X)
- Xiqun Chen (ORCID: https://orcid.org/0000-0001-8582-8891)
- Jackson G. Schumacher (ORCID: https://orcid.org/0009-0000-4227-4710)
- Sarfraz Ahmed (ORCID: https://orcid.org/0000-0001-5879-0461)
- Michael A. Schwarzschild (ORCID: https://orcid.org/0000-0001-6019-8280)
- Jian Wang (ORCID: https://orcid.org/0000-0001-7104-0673)
- Jae Suk Ahn (ORCID: https://orcid.org/0000-0002-9508-4301)
- Yukun Tan (ORCID: https://orcid.org/0000-0002-6368-8653)
- Weiyi Peng (ORCID: https://orcid.org/0000-0002-7785-6240)
- Roshni Jaffery (ORCID: https://orcid.org/0000-0003-4128-345X)
- Jiayin Zhang (ORCID: https://orcid.org/0009-0006-7399-6752)
- Ken Chen (ORCID: https://orcid.org/0000-0003-4013-5279)
- Yuhang Zhao (ORCID: https://orcid.org/0009-0000-9976-3478)
- Yujia Wang (ORCID: https://orcid.org/0000-0002-5264-521X)
- L Shi (ORCID: https://orcid.org/0000-0002-8895-1403)
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- Harvard University (US)
- Massachusetts General Hospital (US)
- Research Network (United States) (US)
- University of Houston (US)
Publication Details
- Journal
- npj Parkinson s Disease
- Published
- 2025-11-27
- DOI
- https://doi.org/10.1038/s41531-025-01215-5
- Primary Topic
- Parkinson's Disease Mechanisms and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Michael J. Fox Foundation for Parkinson's Research
- National Institutes of Health