It is now understood that genetic factors play a crucial role in the risk of developing Alzheimer's disease (AD). Rare mutations in at least 3 genes are responsible for early-onset familial AD. A common polymorphism in the apolipoprotein E gene is the major determinant of risk in families with late-onset AD, as well as in the general population. Advanced age, however, remains the major established risk factor for AD, although environmental variables may also have some role in disease expression. Some pathogenic factors directly associated with aging include oxidative damage and mutations in messenger RNA. Other factors unrelated to the aging process may, in the future, be amenable to therapeutic intervention by way of estrogen replacement therapy for postmenopausal women, anti-inflammatory drug therapy and reducing vascular risk factors. Older theories, such as aluminum playing a role in the pathogenesis of AD, have been mostly discarded as our understanding of pathogenic mechanisms of AD has advanced.