Apolipoprotein E (APOE) plays a significant role during the conversion from cognitive normal (CN) to AD through regulating Amyloid-β peptide (Aβ) metabolism, aggregation, and deposition (Kanekiyo et al., 2014; Mahoney-Sanchez et al., 2016; Belloy et al., 2019), in which ε4 allele of APOE is widely acknowledged as the strongest genetic risk variant for AD (Gharbi-Meliani et al., 2021; Serrano-Pozo et al., 2021). This evidence concerns the gene APOE and Alzheimer disease.