While several major genes contributing to risk of Alzheimer Disease have been identified (APP[3], PS1[4], PS2[5]–[7]), all but one (APOE[8]–[10]) contributed predominantly to early-onset forms of AD that cluster within families; other than APOE, few consistent association signals have been observed for late-onset AD (LOAD). The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.