show Abstracthide AbstractThis work investigated the effect of High-fat diet (HFD) on mouse brain cortices, in APOE3 and APOE4 background. We hypothesized that HFD-induced obesity alters brain transcriptomics in APOE-genotype and sex dependent manners. Six-month-old APOE3-TR and APOE4-TR mice were treated with either HFD or control chow. After 4 months, total RNA was extracted from the cerebral cortices and analyzed by poly-A enriched RNA sequencing on the Illumina platform. Here, we investigated interactions between HFD, APOE, and sex, using a knock-in mouse model of the human APOE3 and APOE4 alleles.