Genetic factors play a major role in some if not all cases of Alzheimer's disease (AD). In certain rare families, the disease is most likely inherited as an autosomal dominant trait. Identification of the genes involved in AD is in progress. One AD-related gene, which codes for the amyloid precursor protein (APP), has been cloned and characterized. This gene, though certainly involved in the pathogenesis of AD, is not defective in AD subjects. Genetic linkage analysis of familial Alzheimer's disease (FAD) should help to identify defective genes directly involved in initiating the pathogenesis of AD. In addition, the study of the genes responsible for the Down syndrome (DS) phenotype may yield information on the sequence of events leading to the dementia of AD.