Whole transcriptome analysis of peripheral blood mononuclear cells from de novo and drug-naive Parkinson's disease patients.

Blood-based biomarkers represent a highly convenient and minimally invasive method to improve the diagnosis of Parkinson's disease (PD), particularly at early stages. In this study, we present a comprehensive analysis of transcriptional changes in peripheral blood mononuclear cells (PBMCs) from de novo and drug-naive, recently diagnosed PD patients (n ​= ​23) and healthy sex- and age-matched controls (n ​= ​16). Whole-transcriptome analysis revealed differentially expressed genes (DEGs) in PBMCs from PD patients, including genes with immune-related functions such as CHI3L1, FAM198B, ID3, MDX1, and PROK2. Gene set enrichment analysis (GSEA) further identified alterations in immune pathways, including the IL-6/JAK/STAT3 signaling pathway and the complement cascade, associated with PD. We performed cross-validation using two independent whole-blood transcriptomic datasets from PD patients to assess the reproducibility and biological relevance of our findings. Both comparisons showed moderate but highly significant correlations in gene expression patterns. Overall, our results reveal robust and reproducible transcriptional alterations in PBMCs from early-stage PD patients, underscoring the contribution of immune dysregulation to PD pathogenesis. These findings support the potential of PBMC transcriptomics as a valuable platform for biomarker discovery in Parkinson's disease.