Cerebrospinal Fluid Neuroinflammatory Biomarkers and Motor Symptom Severity in Early-Stage Parkinson’s Disease: A Cross-Sectional Analysis of the PPMI Cohort

Abstract

Neuroinflammation has been implicated in Parkinson’s disease (PD) pathology, but whether cerebrospinal fluid (CSF) neuroinflammatory biomarkers reflect motor symptom severity in earlystage disease remains unclear. This cross-sectional study examined whether four CSF biomarkers (glial fibrillary acidic protein (GFAP), chitinase-3-like protein 1 (YKL-40), soluble triggering receptor expressed on myeloid cells 2 (sTREM2), and interleukin-6 (IL-6)) correlate with motor severity, measured by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III (MDSUPDRS Part III), in 215 de novo, medication-naive PD patients from the Parkinson’s Progression Markers Initiative (PPMI) cohort. Patients were stratified by Hoehn and Yahr Stage 1 (n = 93) and Stage 2 (n = 122). Spearman correlations, multiple linear regression adjusted for age, sex, and disease duration, and biomarker by stage interaction models were used. No significant interactions were observed. In unadjusted analysis, only sTREM2 correlated with motor severity, and both sTREM2 and YKL-40 were elevated in Stage 2. After covariate adjustment, no biomarker was independently associated with motor scores, and no result survived Benjamini-Hochberg correction. Enrollment age was the only consistent predictor across all models. The sTREM2 association was attenuated after age adjustment and could not be distinguished from age-related covariation. These findings suggest that CSF neuroinflammatory biomarkers were not associated with early motor severity in this sample of early-stage PD patients, and future research should examine whether these markers are more closely associated with other domains such as cognitive decline.