One of these models is a triple mutant line carrying a humanized APOE4 allele and the p.R47H mutation knocked into mouse Trem2 (besides the knock-out allele of the IL-1RAcP gene); the other model also preserves humanized Aβ and APOE4 knock-ins and CRISPR/Cas9-generated APP allele, p.R47H point mutation of the Trem2 gene and deletion of exon 3 of the IL-1RAcP—all intended to increase the risk of late-onset Alzheimer’s disease. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.