Fig. 2
APOE2 drives mitochondrial changes in neurons especially when accompanied by AD pathology. a, b Heatmap showed mitochondrion-associated pathways altered in APOE2 versus APOE3 brain in bulk RNA-seq (a) and altered in excitatory and inhibitory neurons in APOE2 versus APOE3 individuals (b) stratified by amyloid. Red indicated APOE2 upregulation and blue indicated APOE2 downregulation. The color scale represents sign (log [FC]) × log10[P] values. P < 0.05 indicated (x). c, d Box plots showed pathway activity scores for ‘MITOMAP: Nuclear Mitochondrial Genes (147 genes associated with mitochondrion)’ (c) and for ‘GO: ATP synthesis coupled electron’(d) stratified by APOE genotype and/or AD pathology (nominal P-values, linear model). Boxplots indicates median, 25th and 75th percentiles. e Correlation analysis between oxidative phosphorylation pathway scores and the APOE expression values in excitatory neurons (Ex, APOE2: R = 0.41, P < 2.2e−16; APOE2: R = 0.29, P = 2.2e−16), with APOE2 excitatory neurons demonstrating a more significant correlation in comparison to APOE3 (z = 5.7837, P = 0.0000); ****P < 0.0001. f Correlation analysis between oxidative phosphorylation pathway scores and the APOE expression values in inhibitory neurons (In, APOE2: R = 0.56, P < 2.2e−16; APOE2: R = 0.34, P = 2.2e−16), with APOE2 inhibitory neurons demonstrating a more significant correlation in comparison to APOE3 (Z = 11.7636, P = 0.0000); ****P < 0.0001