APOE and obesity due to melanocortin 4 receptor deficiency: Our finding that E3FAD mice did not show a diet-induced increase in AD-related pathology is similar to null findings in some rodent models of obesity (Zhang et al., 2013; Knight et al., 2014; Niedowicz et al., 2014), suggesting that deleterious effects of obesity can be regulated by genetic factors besides APOE4. Thus, these data suggest an important gene X environment interaction in which APOE4 carriers are more susceptible to the AD-promoting effects of obesity.