Four genes involved in the development of Alzheimer disease have been identified. Three fully penetrant (deterministic) genes lead to the development of Alzheimer disease in patients younger than 60 years: the amyloid beta-protein precursor on chromosome 21, presenilin 1 on chromosome 14, and presenilin 2 on chromosome 1. Together, they account for about half of this early-onset form of the disease. One genetic risk factor--apolipoprotein E-4--is associated with late-onset Alzheimer disease. It accounts for a substantial fraction of disease burden but seems to act primarily to lower the age of disease onset. In general, none of these genes can be easily adapted for use as a diagnostic or predictive test for Alzheimer disease. Research activity includes searching for additional genes, especially for late-onset disease, and elucidating the mechanism of action of all identified genes as part of a long-term effort to develop more effective therapeutic and preventive strategies.