Genetic susceptibility factors for Alzheimer's disease.

Alzheimer's disease is the most frequent cause of dementia. Family and twin studies have suggested that genetic factors play a role in Alzheimer's disease development. Some Alzheimer's disease cases show an autosomal dominant inheritance pattern and thus allow the discovery of major disease genes. However, most Alzheimer's disease cases are sporadic. These cases are mainly due to the effects of several different genes and of interactions between genetic susceptibility factors and environmental factors. Such interactions are illustrated by the apolipoprotein E epsilon4 allele, associated with a higher risk of Alzheimer's disease. Other genetic susceptibility factors have been reported but variously confirmed in Alzheimer's disease: apolipoprotein E receptors, alpha2-macroglobulin or angiotensin I converting enzyme genes. Thus, except for a small percentage of Alzheimer's disease cases with a dominant inheritance pattern, the genetic component of the vast majority of cases is underlain by complex interactions of genetic susceptibility factors and environmental conditions.