Fourth, we applied EWCE 11 to test whether genes that are up/down-regulated in human post-mortem Parkinson’s disease brains (from six separate cohorts) were enriched in cell types located in the substantia nigra and ventral midbrain (Figure 5). Three of the studies had a case-control design and measured gene expression in: (a) the substantia nigra of 9 controls and 16 cases 46, (b) the medial substantia nigra of 8 controls and 15 cases 47, and (c) the lateral substantia nigra of 7 controls and 9 cases 47. In all three studies, downregulated genes in Parkinson’s disease were specifically enriched in dopaminergic neurons (consistent with the loss of this particular cell type in disease), while upregulated genes were significantly enriched in cells from the oligodendrocyte lineage. This suggests that an increased oligodendrocyte activity or proliferation could play a role in Parkinson’s disease etiology. Surprisingly, no enrichment was observed for microglia, despite recent findings 48,49.
