Fig. 6

APOE4 and female sex are risk factors for the emergence of FDAMic. A Visualization of APOE status distribution in all subtypes of microglia from the Mathys et al. cohort. B Ratios of nuclei of different APOE statuses in all subclusters of microglia. C Violin plot illustrating the normalized expression level of the APOE gene in all microglial subtypes. D Heatmap illustrating the major trend of changes in gene expression across individuals carrying different combinations of APOE allelic variants. E Violin plots illustrating the expression profiles of key microglial proliferation-associated genes across samples with different combinations of APOE allelic variants. F–H Functional enrichment analysis of the F upregulated DEGs in female subjects carrying APOE-34 or APOE-44 and the G upregulated and H downregulated DEGs in male subjects carrying APOE-34 or APOE-44 compared to subjects of the respective sex with combinations of APOE-22, APOE-23 or APOE-33. I Cell ratio changes in microglial populations of the ROSMAP samples predicted by the Scaden deep learning algorithm. Comparisons were made across either male or female subjects carrying different combinations of APOE allelic variants. J Heatmap illustrates the matching of DEGs in FDAMic (Fig. 3A) to transcriptome profiles of microglia harvested from control or 5xFAD mice in which endogenous ApoE alleles were replaced by either human APOE3 (i.e., 33) or APOE4 (i.e., 44)