Besides, ApoE4 not only affects secreted ectodomain APPα (sAPPα) secretion (Cedazo‐Minguez et al., 2001; Vincent & Smith, 2001) but also directly regulates Sirtuin1 protein expression and enzyme activity (Theendakara et al., 2016), which is related to programmed cell death, insulin resistance, and synaptic function, all of which are involved in AD pathogenesis (Theendakara et al., 2018). This evidence concerns the gene APOE and Alzheimer disease.