Since both human astrocytes and microglia from APOE4/4 carriers have decreased lipid clearance, enhanced cholesterol accumulation, and higher production of extracellular matrix protein and proinflammatory cytokines than their APOE3/3 counterparts (Tcw et al., 2022), this suggest that APOE4 may drive both cell types toward an AD state, especially in microglia that express more APOE in the context of AD. Here, APOE is linked to Alzheimer disease.