The generation of mice carrying a mutant ApoE gene or different ApoE isoforms, such as ApoE knockout (ApoE KO) and humanized ApoE knockin (hApoE KI) mice [17,18,19,20,21], provides powerful tools for studies of lipid metabolism, Alzheimer’s disease, and cardiovascular diseases (CVDs), including atherosclerosis and CHD. This evidence concerns the gene APOE and early-onset autosomal dominant Alzheimer disease.