The genetics of Alzheimer's disease: a review and a discussion of the implications.

This paper examines the evidence for a genetic etiology of Alzheimer's Disease. Three groups of cases are identified; the first being those with a consistently early age of onset, in which autosomal dominant inheritance can be established. These families may require genetic counseling, and represent an extraordinary resource for research. There are early onset cases without a strong genetic component, and later onset cases generally show only weak evidence of hereditary disease. Some of the apparent distinctions between these groups may result from methodologic problems, especially if the age of onset of symptoms is highly variable in the majority of families. Studies of associations between Alzheimer's Disease and Down's Syndrome suggest a role for genes on chromosome 21 in the genesis of the pathologic features, and testable hypotheses can be identified. Attempts to link the development of Alzheimer's Disease to the presence of specific inherited markers have generally been unsuccessful to date, but there are some promising findings. Recent progress in understanding the molecular basis of other inherited diseases is reviewed in relation to attempts to understand the possible molecular basis of Alzheimer's Disease. A limiting factor in future studies will probably be the availability of cells and tissues from pedigrees demonstrating autosomal dominant inheritance of this disorder.