APOE and Alzheimer disease: Specifically, the late onset Alzheimer’s disease (LOAD1) mouse model of AD, a transgenic model double homozygous for APOE4 and Trem2 R47H mutation additionally combined with the M28L variant of phospholipase C Gamma 2 (Plcg2) or the 677C > T variant in methylenetetrahydrofolate reductase (Mthfr), was fed with a 45% fat and 36% carbohydrate diet for 10 months, beginning at 2 months of age.