Alzheimer’s disease is found in the alpha/beta-hydrolase fold protein gene NDRG family member 2 (NDRG2) (P < 5.6 × 10−19; β=−0.058) and is also associated with measures of both amyloid and Tau pathology (Fig. 2c). Differential splicing of both PFKP and NDRG2 in human brains has been previously shown to be associated with Alzheimer’s disease pathogenesis22,23, offering a measure of replication. Other genes with differentially excised introns associated with Alzheimer’s disease at a Bonferroni-corrected P < 0.05 include APP (P < 1.6 × 10−3; β=−0.003) and genes in known GWAS loci including PICALM (P < 0.02; β=0.005) and CLU (P < 3.2 × 10−4; β=−0.019). These differential splicing genes are not necessarily expressed in a single cell type (e.g., neurons) but are expressed across many cell types including astrocytes (Supplementary Figs. 2 and 3; Supplementary Table 4). Moreover, co-splicing network analysis using WGCNA24 suggests that the differentially spliced genes are enriched in specific functional modules and are part of a coherent biological process (Supplementary Figs. 2 and 3; Supplementary Tables 5–7; Supplementary Note).
