The genetics of Alzheimer's disease

Prog Neurobiol. 1997 Aug;52(6):447-54. doi: 10.1016/s0301-0082(97)00014-2.


Alzheimer's disease (AD) is the major cause of dementia in the U.K. The clinical diagnosis of the specific disease resulting in dementia is unreliable and thus a definitive diagnosis of AD is best made in conjunction with post-mortem findings of amyloid plaques and neurofibrillary tangles. Alzheimer's disease is neuropathologically indistinguishable in the young and old, but has been divided arbitrarily into early- and late-onset disease using age cut-offs of 60 or 65 years. Twin and family studies suggest that genetic factors play a major role in its aetiology. This review considers the three loci which have been shown to be associated with early-onset AD: amyloid precursor protein, presenilin (PS)-1 and PS-2. Mutations in these genes seem to be associated with overproduction of the 42-amino acid form of beta-amyloid, suggesting that this may be a central pathological process in AD. The impact of the different apo E alleles on the risks for late- and early-onset AD is discussed and compared with other dementing conditions. Recent analyses suggest that there are likely to be other genes besides apo E which impact on late-onset AD risk. The possible roles in AD of the mitochondrial mutation at position 4336, the PS intron 8 polymorphism, and variants in the alpha 1-antichymotrypsin and VLDL-receptor genes, are considered.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Apolipoproteins E / genetics
  • Dementia / genetics
  • Genotype
  • Humans
  • Membrane Proteins / genetics
  • Presenilin-1


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