A preliminary analysis of the inflammatory protein landscape in the CSF of mid- to late-stage Parkinson’s disease: associations with motor severity and subtypes

Purpose Parkinson’s disease (PD) is a progressive neurodegenerative disorder in which neuroinflammation is recognized as a contributor to clinical progression. This study aimed to characterize the cerebrospinal fluid (CSF) inflammatory profile in mid- to late-stage PD patients and identify specific inflammatory proteins with potential clinical relevance to motor symptoms and disease severity. Methods In this preliminary retrospective cross-sectional study, CSF samples were obtained from 25 patients with mid- to late-stage PD undergoing evaluation for deep brain stimulation (DBS) (mean disease duration: 10.24 ± 4.65 years) and 15 non-PD controls (essential tremor or dystonia) undergoing identical surgical procedures. The levels of 92 inflammation-related proteins were quantified using the Olink proximity extension assay (PEA). Based on the identified differentially expressed proteins (DEPs), we next performed preliminary exploratory comparisons of inflammatory profiles between the postural instability and gait difficulty (PIGD, n = 10) and tremor-dominant (TD, n = 10) PD subtypes. Additionally, preliminary correlation analyses were performed between the DEPs and Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part-III (MDS-UPDRS-III) scores to generate preliminary observations with limited clinical inference. Results Using the Olink platform, 28 DEPs were identified between the PD and non-PD groups ( p < 0.05). Subsequent protein-protein interaction network analysis identified IFN-γ as the central hub. Exploratory descriptive analyses of TD and PIGD subgroups are provided in Additional file 1: Supplementary Figure S1. Among all DEPs, IL-10RB ( r = 0.440, 95% CI [0.054, 0.711], p = 0.028), CD8A ( r = 0.415, 95% CI [0.024, 0.696], p = 0.039), and CXCL9 ( r = 0.414, 95% CI [0.023, 0.696], p = 0.040) showed moderate correlations with MDS-UPDRS-III scores. Conclusion In profiling 92 CSF inflammation-related proteins from 25 advanced PD patients (Hoehn–Yahr 3–4) and 11 controls, we identified 28 upregulated DEPs. IFN-γ emerged as a topologically connected hub in protein-protein interaction networks, and three proteins (IL-10RB, CD8A, CXCL9) showed moderate correlations with motor scores. As cross-sectional descriptive observations, these findings establish a preliminary framework to generate hypotheses for future mechanistic validation and biomarker discovery, while no functional causality can be inferred from the present results.