Note! This is a brief overview of the molecular genetics of Alzheimer disease. Detailed information for lay persons, caregivers, physicians and researchers can be found on the web sites listed in the Links Section.
Alzheimer disease (AD, OMIM entry 104300) is the most common form of dementia. In 25 to 40% of AD patients genetic factors are involved and in some cases, AD segregates as an autosomal dominant trait in families. In these families, 3 genes are identified that, when mutated, cause AD: the Aβ amyloid precursor protein gene (APP), the presenilin 1 gene (PSEN1) and the presenilin 2 gene (PSEN2). Together, these mutations are responsible for 30 to 50% of autosomal dominant AD cases, and about 0.5% of AD in general. Although mutations in the known genes are a rare cause of AD, they are important for in presymptomatic diagnostics of patients of autosomal dominant AD families that segregate these mutations. Also, the identification of these genes and mutations has been extremely important to the recent progress in the understanding of the biology of AD. In cases where the inheritance pattern is unclear and in sporadic cases the ε4 allele of the apolipoprotein E gene (APOE) was identified as a major risk factor contributing to the pathogenesis of AD in about 20% of the cases. However, other causative and risk genes are involved in AD and need to be identified to fully elucidate the etiology of AD. Ultimately, this will lead to the development of effective therapies for this major disease.