Molecular genetics of Alzheimer's disease

Ann Med. 1998 Dec;30(6):560-5. doi: 10.3109/07853899809002605.

Abstract

Genetic factors are involved in the aetiology of Alzheimer's disease (AD) in 25-40% of the cases. In some cases AD clearly segregates as an autosomal dominant trait in families. Three genes have been identified which, when mutated, cause AD: the Abeta amyloid precursor protein gene (APP), and the presenilin-1 (PSEN1) and presenilin-2 (PSEN2) genes. Together, these mutations are responsible for 30-50% of the cases with autosomal dominant AD, and for about 5% of AD in general. In cases where the inheritance pattern is unclear and in sporadic cases the epsilon4 allele of the apolipoprotein E gene (APOE) has been identified as a major risk factor contributing to the pathogenesis 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 presymptomatic diagnostics in autosomal dominant AD families that segregate these mutations. Also, the identification of these genes and mutations has been extremely 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. This will ultimately lead to the development of effective therapies for this major disease.

Publication types

  • Review

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Apolipoproteins E / genetics
  • Chromosomes, Human, Pair 1
  • Chromosomes, Human, Pair 14
  • Chromosomes, Human, Pair 19
  • Chromosomes, Human, Pair 21
  • Genetic Linkage
  • Humans
  • Membrane Proteins / genetics
  • Presenilin-1
  • Presenilin-2

Substances

  • Amyloid beta-Protein Precursor
  • Apolipoproteins E
  • Membrane Proteins
  • PSEN1 protein, human
  • PSEN2 protein, human
  • Presenilin-1
  • Presenilin-2