We thus analyzed human apoE-targeted replacement (apoE-TR) (Sullivan et al., 1997; Sullivan et al., 1998; Knouff et al., 1999) and Apoe-knockout (KO) mice (Piedrahita et al., 1992) to examine whether the effects of APOE on lifespan can indeed be observed in the absence of AD. The gene discussed is APOE; the disease is Alzheimer disease.