The ApoE4 genotype has also been implicated in the effects of obesity on AD, whereby a high-fat diet increased Aβ pathology in the familial AD (FAD) mouse model expressing ApoE4 but not ApoE3 [211], and was shown to worsen the cognitive decline associated with insulin resistance [212]. Here, APOE is linked to obesity due to melanocortin 4 receptor deficiency.