While several genetic risk factors for late-onset Alzheimer's disease have been identified and replicated in independent studies, including the ApoE ε4 allele, the great majority of the heritability of late-onset Alzheimer's disease remains unexplained, likely due to the aggregate effects of a very large number of genes with small effect size, as well as to biases in sample collection and statistical approaches. The gene discussed is APOE; the disease is early-onset autosomal dominant Alzheimer disease.