Deciphering the genetic basis of Alzheimer's disease

Annu Rev Genomics Hum Genet. 2002;3:67-99. doi: 10.1146/annurev.genom.3.022502.103022. Epub 2002 Apr 15.


A remarkable rise in life expectancy during the past century has made Alzheimer's disease (AD) the most common form of progressive cognitive failure in humans. Compositional analyses of the classical brain lesions, the senile (amyloid) plaques and neurofibrillary tangles, preceded and has guided the search for genetic alterations. Four genes have been unequivocally implicated in inherited forms of AD, and mutations or polymorphisms in these genes cause excessive cerebral accumulation of the amyloid beta-protein and subsequent neuronal and glial pathology in brain regions important for memory and cognition. This understanding of the genotype-to-phenotype conversions of familial AD has led to the development of pharmacological strategies to lower amyloid beta-protein levels as a way of treating or preventing all forms of the disease.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / genetics*
  • Amino Acid Sequence
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Protein Precursor / genetics
  • Apolipoproteins E / genetics
  • Chromosome Mapping
  • Genotype
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation, Missense
  • Presenilin-1
  • Receptors, Notch
  • Signal Transduction


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