Identifying Immune Response Protein Biomarkers in Parkinson’s-Related Cognitive Impairment and Depression

A distinct immune microenvironment may develop in patients with Parkinson’s disease (PD), influenced by the severity of cognitive impairment and the presence of depression. We aimed to identify blood-based immune response markers in patients with PD using a proximity extension assay (PEA). Peripheral plasma samples from 58 patients with PD and 30 healthy controls (HCs) were analyzed for 92 immune response-associated proteins using Olink’s PEA technology. A panel of four proteins (SIT1, CLEC4C, EIF5A, and NFATC3) was identified, effectively differentiating patients with PD from HCs, with a combined area under the receiver operating characteristic (ROC) curve of 0.863. Among these, ITGA11 and EIF5A were particularly associated with the degree of cognitive impairment. After applying Bonferroni correction, five proteins—PPP1R9B, MILR1, BTN3A2, IRAK1, and TANK—demonstrated potentially significant differences between depressed and non-depressed patients with PD-cognitively normal (PD-CN). In the correlation analyses, PPP1R9B exhibited a positive correlation with the Hamilton Depression Rating Scale (HAMD) score (r = 0.509, P = 0.019). Furthermore, after adjusting for potential confounding factors in binary logistic regression analysis, PPP1R9B remained significantly associated with depression (P = 0.042). We identified potential blood-based immune response markers associated with the severity of cognitive impairment and depression in patients with PD. These findings provide preliminary insights into the immune-related pathology underlying non-motor symptoms of PD, potentially guiding future studies aimed at targeted therapeutic strategies. Further validation in larger, independent cohorts is warranted to confirm these associations and their clinical utility.