Molecular genetics of Alzheimer's disease

Genetic factors are involved in the aetiology of Alzheimer's disease (AD) i n 25-40% of the cases. In some cases AD dearly segregates as an autosomal d ominant trait in families. Three genes have been identified which, when mut ated, cause AD: the A beta amyloid precursor protein gene (APP), and the pr esenilin-1 (PSEN1) and presenilin-2 (PSEN2) genes. Together, these mutation s are responsible for 30-50% of the cases with autosomal dominant AD, and f or about 5% of AD in general. In cases where the inheritance pattern is unc lear and in sporadic cases the epsilon 4 allele of the apolipoprotein E gen e (APOE) has been identified as a major risk factor contributing to the pat hogenesis of AD in about 20% of the cases. Although mutations in the known genes are a rare cause of AD they are useful for the purposes of presymptom atic diagnostics in autosomal dominant AD families that segregate these mut ations. Also, the identification of these genes and mutations has been extr emely important to the recent evolution in the understanding of the biology of the disease. However, other causative and risk genes are involved in AD and need to be identified in order to fully elucidate the biology of AD. T his will ultimately lead to the development of effective therapies for this major disease.