Genetic and environmental factors in Alzheimer's disease

In recent years, considerable progress has been made in unraveling the etio logy of Alzheimer's disease (AD). Dominant mutations have been identified, in the beta-amyloid precursor protein gene (APP), and in two homologous gen es presenilin 1 (PSEN-1) and presenilin 2 (PSEN-2). The contribution of the se mutations to the occurrence of AD in the general population is estimated to be lower than 1p.100. A genetic risk factor of more importance on the p opulation level is the Apolipoprotein E (APOE) gene that may explain up to 17p.100 of the prevalence of AD in the general population. It is clear that other yet unknown genes must be involved in the etiology of AD. Two loci o n chromosome 12 have been suggested, but no consistent effect could be foun d, Important progress with regard to non-genetic risk factors concerns the role of vascular and endocrine factors in the pathogenesis, Of major intere st for the prevention of AD will be the interaction of genetic and non-gene tic risk factors. Large scale, long term follow-up studies, ongoing at pres ent, may clarify this issue.