EIF2A and Alzheimer disease: For example, amounts of phosphorylated eIF2α increase with normal aging in wild-type mice, while mice overexpressing human apolipoprotein E4 (ApoE4: a strong genetic risk factor that modulates the prevalence, age of onset and the burden of pathology in sporadic AD) show elevations in eIF2α phosphorylation in brains and deficient learning and memory, as compared with age-matched ApoE3 control mice (Segev et al., 2013).