Neuroinflammation plays a crucial role in the pathogenesis of Parkinson's disease: a systematic review and meta-analysis of clinical and biomarker evidence.

OBJECTIVE

Clarifying whether circulating cytokines differ between individuals with PD and healthy controls may improve understanding of peripheral immune involvement in PD and support the development of potential biomarkers.

METHODS

We conducted a systematic review and meta-analysis following PRISMA 2020 guidelines. Case–control studies reporting quantitative serum or plasma inflammatory biomarkers in PD were identified through multiple databases. Standardized mean differences (Hedges’ g) were pooled using random-effects models with Hartung–Knapp adjustment. Subgroup analyses, meta-regression (age and sample size), publication bias assessment, and leave-one-out sensitivity analysis were performed.

RESULTS

Eight studies met the inclusion criteria. The overall pooled effect showed no significant difference in peripheral inflammatory biomarker levels between PD and controls (SMD = 0.18, 95% CI − 0.71 to 1.08; I² = 96.9%). Subgroup analyses revealed marker-dependent heterogeneity, with inconsistent findings for IL-6, TNF-α, and IL-8. Meta-regression identified age as a positive moderator and sample size as a negative moderator of effect size. Funnel-plot asymmetry suggested potential publication bias or small-study effects. Sensitivity analyses confirmed the robustness of the overall null result.

CONCLUSION

Current evidence does not support a consistent alteration of peripheral cytokine and chemokine levels in PD. The substantial heterogeneity and moderating effects of age and sample size indicate that circulating cytokines alone do not reliably reflect the complexity of immune dysregulation in PD. Future studies should adopt standardized assay procedures, comprehensive immune profiling beyond soluble mediators, stratified designs, and longitudinal approaches to better characterize PD-related immune alterations.