Regarding microgliosis and astrocytosis, we found E4-driven microgliosis in E4 and E4NLF mice (Figs. 1b and 1e; Supplemental Fig. 1d and 1e), and NLF-driven astrocytosis in NLF and E4NLF mice (Fig. 1f), suggesting a pathogenic divergence between APOE4 and Aβ in driving distinct AD-related pathological changes in early disease pathogenesis, consistent with human transcriptomic data29,37. This evidence concerns the gene APOE and Alzheimer disease.