Recent advances in the genetics of Alzheimer's disease and vascular dementia with an emphasis on gene-environment interactions

OBJECTIVE: To review recent findings in the genetics of Alzheimer's disease (AD) and vascular dementia (VaD) with particular emphasis on gene-environment interactions. DESIGN: A survey and critique of recent literature on the genetic etiology of AD and VaD. CONCLUSIONS: Recent research has identified several genes associated with AD, including loci on chromosome 1, 14, 19, and 21. Two of these loci, encoding the beta-amyloid precursor protein and apolipoprotein E, have gene products that are well characterized and of evident significance in the pathogenesis of AD. The four genes together probably account for little more than 50% of all cases of AD, but other undiscovered loci are likely. Interaction of genetic effects with environmental influences may affect both onset and expression of AD. By contrast, only a small minority of VaD cases can be attributed to a pure genetic etiology. The majority of VaD is caused by both genetic and environmental factors. Many of the environmental antecedents also have genetic determinants (e.g., smoking). Knowledge of the gene-environment interactions for both AD and VaD will facilitate identification of early preclinical symptoms of disease, a stage of the disease process during which treatment may be most beneficial.