Seminar · Molecular Neuroscience
Cholesterol and matrisome pathways dysregulated in Alzheimer’s disease brain astrocytes and microglia
Julia TCW · Boston University
Fri, Dec 16, 2022 · 06:00 UTC
The impact of apolipoprotein E ε4 (APOE4), the strongest genetic risk factor for Alzheimer’s disease (AD), on human brain cellular function remains unclear. Here, we investigated the effects of APOE4 on brain cell types derived from population and isogenic human induced pluripotent stem cells, post-mortem brain, and APOE targeted replacement mice. Population and isogenic models demonstrate that APOE4 local haplotype, rather than a single risk allele, contributes to risk. Global transcriptomic analyses reveal human-specific, APOE4-driven lipid metabolic dysregulation in astrocytes and microglia