APOE and Alzheimer disease: Whatever the precise mechanism, APOE-ɛ4 carriers have a much increased risk of developing sporadic AD (Corder et al., 1993), of progression to AD if diagnosed with mild cognitive impairment (MCI) (Petersen, 1995), and to develop AD at an earlier age (Corder et al., 1993; van der Flier et al., 2011) compared to non-carriers.