APOE and Alzheimer disease: Although it has been established that specific allelic variants in the APOE gene are associated with risk for late-onset AD,12 it is less clear whether other allelic variants of the APOE gene impart healthy cognitive function.13, 14 However, APOE polymorphisms have been shown to exert divergent neuroprotective effects.15, 16 For example, the presence of APOE ɛ4 is associated with an increased rate of AD-related hippocampal atrophy17 and impaired synaptic plasticity18 when compared with APOE ɛ4 noncarriers.