Is there a genetic basis for the deposition of beta-amyloid after fatal head injury?

Cell Mol Neurobiol. 1999 Feb;19(1):19-30. doi: 10.1023/a:1006956306099.

Abstract

1. Alzheimer's disease is a heterogeneous disorder that may be caused by genetic or environmental factors or by a combination of both. Abnormalities in chromosomes 1, 14, and 21 have all been implicated in the pathogenesis of the early-onset form of the disease, while the epsilon 4 allele of the apolipoprotein E gene (on chromosome 19) is now recognized as a risk factor for early- and late-onset sporadic and familial Alzheimer's disease. 2. The best-established environmental trigger for the disease is a head injury, based on epidemiological and neuropathological evidence. Approximately 30% of patients who die after a single episode of severe head injury show intracerebral deposition of beta-amyloid protein (A beta), a protein that is thought to be central to the pathogenesis of Alzheimer's disease. 3. Recent studies have revealed an over-representation of the apoE epsilon 4 allele in those head-injured patients displaying A beta pathology, thus providing the first evidence for a link between a genetic susceptibility (apoE epsilon 4) and an environmental trigger (head injury) in the development of Alzheimer-type pathology.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Protein Precursor / metabolism
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Brain / metabolism
  • Child
  • Child, Preschool
  • Craniocerebral Trauma / metabolism*
  • Craniocerebral Trauma / mortality
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Risk Factors
  • Up-Regulation

Substances

  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Apolipoprotein E4
  • Apolipoproteins E