The genetics of Alzheimer's disease

Curr Psychiatry Rep. 2000 Apr;2(2):158-64. doi: 10.1007/s11920-000-0061-z.


Alzheimer's disease (AD) is a genetically complex disorder. Mutations in the amyloid precursor protein and presenilin 1 (PS1) genes are fully penetrant and cause early-onset AD. Mutations in presenilin 2, a PS1 homologue, cause partially penetrant autosomal dominant AD with onset age beginning at 40 years and extending past 75 years. A fourth gene, apolipoprotein E (ApoE) is a risk-factor for late-onset AD. Over 40 genes have been tested as AD candidate genes, yet none has been clearly established as an AD risk factor. Linkage studies have implicated a number of chromosome regions as possible sites for late-onset AD loci with the strongest evidence being for chromosome 12. Candidate genes in this region include alpha2-macroglobulin (A2M) and low-density lipoprotein receptor-related gene (LRP), although neither has been clearly established as an AD gene. Identification of additional late-onset genes will require larger samples, more sophisticated analysis methods, and large-scale positional cloning efforts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Amyloid beta-Protein Precursor / genetics
  • Apolipoproteins E / genetics
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12 / genetics
  • Gene Expression
  • Genetic Markers
  • Humans
  • Membrane Proteins / genetics
  • Point Mutation / genetics
  • Presenilin-1
  • Presenilin-2
  • alpha-Macroglobulins / genetics


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