Genetic testing for Alzheimer's disease: how close is reality?

Three genes in which mutations cause the early-onset autosomal dominant for m of Alzheimer's disease have been identified. These are the amyloid precur sor protein gene on chromosome 21,the presenilin-1 gene on chromosome 14, a nd the presenilin-2 gene on chromosome 1. Mutations in any of these genes c ause an enhanced production of the long form of beta-amyloid. There is one established susceptibility gene, the apolipoprotein E gene, in which the ep silon 4 allele causes an increased risk of developing Alzheimer's disease. Other potential susceptibility genes for Alzheimer's disease have also been identified, but their importance has to be further established. At present , genetic testing is only warranted in early-onset forms of Alzheimer's dis ease with a familiar clustering. This testing needs strong ethical consider ation. Testing for the apolipoprotein E genotype may aid in the clinical di agnosis of Alzheimer's disease, but should not be performed as a screening tool in nonsymptomatic patients. (C) 1999 Lippincott Williams & Wilkins.