Association between serum inflammatory cytokines, substantia nigra structural changes, and brain functional network in Parkinson's disease.

Background: Parkinson's disease (PD), a common neurodegenerative disorder, involves neuroinflammation and abnormal brain structure and function in its pathogenesis. However, integrative studies of multidimensional biomarkers remain limited. This article aimed to explore the associations between peripheral inflammation levels, substantia nigra (SN) structural changes, and brain functional network features in patients with PD.

Methods: A total of 156 PD participants and 89 healthy participants were enrolled. Transcranial sonography features of SN hyperechogenicity (SN+) were assessed. Functional connectivity density of the putamen, caudate nucleus, posterior cingulate cortex (PCC), and medial prefrontal cortex (mPFC) was analyzed.

Results: In the PD group (AG), serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were markedly elevated and moderately positively correlated with the area of SN+ (p <0.01). The proportion of SN+ in the AG (61.5%) was markedly elevated as against the control group (BG) (24.7%). The functional connectivity density values of the putamen, caudate nucleus, PCC, and mPFC were markedly reduced in the AG (p <0.05), with the functional connectivity density values of the putamen and mPFC negatively correlated with the area of SN+. The functional connectivity of the putamen and mPFC was further weakened in patients with SN+ (p <0.05), indicating a close relationship between SN structural changes and functional damage in motor and cognitive networks.

Conclusion: This article reveals the multidimensional interplay between inflammation, SN structural abnormalities, and brain functional network disruptions in PD patients.