Exploring the dynamic pathogenesis of Parkinson's disease by case-control and longitudinal blood transcriptome analyses

The pathogenesis of Parkinson's disease (PD) was recently hypothesized to change along with the disease course. Given the fact that transcriptional changes in blood can provide insightful clues for PD pathogenesis, we performed case-control and longitudinal whole blood transcriptome analyses to identify the signature genes underlying the hypothesized dynamic pathogenesis of PD. In the case-control study, we compared the gene expression patterns in healthy control (N = 189), prodromal (N = 58) and de novo idiopathic PD subjects (N = 390). The results showed that the prodromal subjects were at the tipping-point stage, which is characterized by the abnormal expression patterns of 414 genes associated with oxygen transport and reactive oxygen species metabolic process. We next performed a longitudinal transcriptome analysis on 255 PD patients from the baseline to the third year, and identified 203 genes related to immune and inflammatory responses during disease progression. These findings not just offer deeper insights into the dynamic pathogenesis of PD, but also help to find potential drugs to prevent the early neurodegeneration process.