The Genetics of Alzheimer Disease and the Application of Molecular Tests

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Abstract
Two general classes of genes are associated with the development of Alzheimer disease (AD). The first group consists of genes that appear to cause AD when mutated, and the second category is composed of genes that are statistically associated with AD, depending on the inheritance of specific alleles. This paper reviews the current state of knowledge about the genetics of AD, and we then discuss the two molecular tests that are currently commercially available. These include a genetic test for mutations in the presenilin 1 (PS1) gene that can diagnose or predict a subset of early onset familial AD with a high degree of certainty. The value of the genetic test for the apolipoprotein (APOE) allele status is far less clear. Inheritance of the ε4 allele is associated with an increased risk of AD at a population level, but APOE genotyping is inappropriate for prediction of future disease in an individual and offers only a marginal increase in diagnostic certainty when symptomatic individuals are tested. In the future, genetic tests may become more broadly applicable to the diagnosis and prediction of AD. However, the utility of such tests is currently limited to a small subset of individuals because in the vast majority of AD cases no clear genetic or environmental cause has been defined.