Alzheimer disease (AD)-like neuropathology increases progressively during aging in most primates, and, in some species, is concurrent with reproductive decline in females and cognitive impairments. We consider how the schedule of AD may have evolved in early humans in relation to the apolipoprotein E (apoE) allele system, which is not found in other primates, and to the increasing duration of postnatal care. The delay of independence and the increasing length of maturation required that the schedule of AD-like neurodegeneration be slowed, otherwise parental caregivers would already have become impaired. We hypothesize that the uniquely human apoE epsilon3 allele evolved from the epsilon4 of primate ancestors during human evolution in relation to the rapid increases of brain size and the emergence of grandmothering. In discussing theses possibilities, we review the diverse bioactivities of apoE, which include involvement in hormone systems. The evolution of menopause is also considered in relation to the protective effect of estrogen on AD.