In addition to the expression of individual genes, we analyzed non-neurological brains from the AHBA to examine the expression of gene sets that may jointly affect the vulnerability of brain regions to PD. To study genetic coherence in vulnerable brain regions, we clustered all 20,017 genes into 167 modules based on their pairwise co-expression across regions R1–R6. The module eigengene, which summarizes the overall expression of genes within a module, was correlated with the labels of regions R1–R6 as defined by Braak stages (Fig. 3a and Supplementary Data 6). Whether or not the modules showed expression patterns that correlated with Braak stages, their expression in the arcuate nucleus of medulla, locus coeruleus and CA2-field was consistently low (Fig. 3b and Supplementary Fig. 7). For the CA2-field this might be explained by the presence of Lewy neurites rather than LBs18. Correlations with Braak stages were mostly driven by the expression change between regions involved in preclinical stages (R1–R3) and clinical stages (R4–R6). In addition, regions R1–R3 showed more extreme expression values (high and low) than in regions R4–R6.
