In the context of disease, APOE was identified more than two decades ago as a significant modulator of the risk for late-onset AD (Wisniewski & Frangione, 1992; Corder et al, 1993, 1994; West et al, 1994; Hyman et al, 1996; Lippa et al, 1997). Here, APOE is linked to Alzheimer disease.