Study overview.Differential vulnerability to Parkinson’s disease (PD) was examined across brain regions R1–R6 (image credit: Allen Institute). N is the number of samples across all six non-neurological donors from the Allen Human Brain Atlas (AHBA), which are involved in the six PD Braak stages as they sequentially accumulate Lewy bodies during disease progression (Supplementary Table 1 and Supplementary Fig. 1). Through correlation and differential expression analysis, we identified Braak stage-related genes (BRGs) with expression patterns that are either positively (r > 0) or negatively (r < 0) correlated with Braak stages in the non-neurological brain. These were validated in cohorts of non-neurological individuals and subsequently in PD patients and age-matched controls. To obtain a more global view of BRG expression signatures, we focused on co-expression modules of all genes and correlated the module eigengene expression with Braak stages. The resulting modules of genes were subsequently analyzed to detect common biologically meaningful pathways.
