APOE and Alzheimer disease: Immune regulatory pathways in iAstrocytes at baseline were negatively enriched in APOE2 versus E3, highly positively enriched in APOE4 versus E3, and moderately enriched in APOE4 versus E2. Two pathways related to TGF-β signaling were highly downregulated APOE4, in line with a study showing dysfunction in TGF-β signaling in models of early AD and in human AD brain (Tesseur et al., 2006), likely connected to its neuroprotective role.