APOE and Alzheimer disease: In AD, there are 1) central insulin resistance resulting from reduction of insulin receptors and desensitization of insulin receptors in neurons [18]–[21], 2) Aβ induced microglial and astrocytic activation and release of inflammatory mediators which lead to neuroinflammation [22]–[24], 3) inhibition of enzymes for mitochondrial oxidative phosphorylation by Aβ leads to increased production of reactive oxygen species (ROS) which cause oxidative stress [25]–[26], and 4) the risk of apolipoprotein E (ApoE) ε4 allele.