Role of proinflammatory biomarkers in Parkinson's disease with non-motor symptoms: A systematic review and meta-analysis

Abstract

Background and objectives. Neuroinflammation, characterized by microglial activation and elevated proinflammatory cytokines, plays a crucial role in Parkinson's disease (PD) pathogenesis and is linked to neurodegeneration and non-motor symptoms. This review aims to identify specific biomarkers associated with these non-motor symptoms, highlighting their roles and implications in PD management and therapy. Materials and methods. This systematic review followed PRISMA guidelines to assess proinflammatory biomarkers in PD patients with non-motor symptoms. We included 10 studies identified through comprehensive searches in PubMed/Medline, Wiley Online Library, Science Direct, Google Scholar, and Neurona. Bias was assessed using the ROBINS-I tool, and study quality was evaluated with GradePro. Meta-analysis was conducted using the Ordmeta test. Results. Proinflammatory biomarkers such as IL-6, TNF-α, CRP, and hs-CRP are notably associated with non-motor symptoms in PD. TNF-α shows a moderate correlation with depressive disorders in 194 patients (p=0.007±0.011), while IL-17A correlates similarly with anxiety, and IL-2 with mood disorders. Furthermore, TNF-α has a low yet meaningful correlation with sleep disorders. Ordmeta results reveal significant elevations of TNF-α in 52 PD patients with cognitive impairment (p=0.0003) and of IL-6 in 361 PD patients (p=0.023±0.008), underlining their roles in PD pathology. Conclusions. This study confirms that proinflammatory biomarkers such as CRP, hs-CRP, IL-6, IL-2, IL-17A, and TNF-α are significantly linked to non-motor symptoms in PD. TNF-α is notably elevated in patients with cognitive impairments and depressive disorders, while IL-6 is also significantly increased in those with cognitive issues.