APOE4-targeted replacement mice, expressing the human APOE4 allele instead of the mouse Apoe, crossed with different AD mouse models such as PDAPP, APP/ PS1ΔE9 and 5xFAD, accelerated plaque formation compared to APOE3-targeted replacement mice (Bales et al, 2009; Castellano et al, 2011; Fagan et al, 2002; Holtzman et al, 2000a; Rodriguez et al, 2014; Youmans et al, 2012). This evidence concerns the gene APOE and Alzheimer disease.