APOE and Alzheimer disease: Broadly speaking, APOE has three main isoforms (E2, E3, and E4) of which APOE4 has been reported to increase the risk as well as decrease the median age of AD onset whereas APOE2 has been demonstrated to mitigate the onset and age-related progression of AD (Bales et al., 1997; Castellano et al., 2011).