APOE4 is associated with increased microglial reactivity to Aβ in deep layers of the cortex. Morphological profiles of reactive microglia within deep cortical Aβ plaque domains were elevated in E4FAD mice. (A) Representative double-stained images of Aβ plaques and microglial activation in deep layers of EFAD cortices (n = 4 or 5 mice/APOE genotype). Scale bar: 30 μm. (B) Left: E4FAD and E2FAD mice exhibited increased reactive microglial density within Aβ plaque domains. Center: Fluorescence intensity of the microglia was elevated in E4FAD mice relative to E3FAD mice. Right: E4FAD microglia occupied a larger percentage of plaque domains than E3FAD microglia. One-way ANOVA, * P < 0.05, ** P < 0.01.