Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury

Nat Med. 1995 Feb;1(2):135-7. doi: 10.1038/nm0295-135.


Deposition of amyloid beta-protein (A beta) in the brain plays a key role in the pathogenesis of Alzheimer's disease. Apolipoprotein E epsilon 4 allele (apo E-epsilon 4) is a strong risk factor for Alzheimer's disease, and there is in vitro evidence that apo E is directly involved in A beta deposition. Head injury is an epidemiological risk factor for Alzheimer's disease and deposition of A beta occurs in approximately one-third of individuals dying after a severe head injury. We report here that the frequency of apo E-epsilon 4 in those individuals with A beta deposition following head injury (0.52) is higher than in most studies of Alzheimer's disease, while in those head-injured individuals without A beta deposition the apo E-epsilon 4 frequency (0.16) is similar to controls without Alzheimer's disease (P < 0.00001). This finding provides further evidence linking apo E-epsilon 4 with A beta deposition in vivo and suggests that known environmental and genetic risk factors for Alzheimer's disease may act additively. In addition our finding indicates a genetic susceptibility to the effects of a head injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Alleles
  • Alzheimer Disease / etiology
  • Amyloid beta-Peptides / analysis*
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Cerebral Cortex / chemistry*
  • Cerebral Cortex / pathology
  • Craniocerebral Trauma / metabolism*
  • Craniocerebral Trauma / pathology
  • Gene Dosage
  • Gene Frequency
  • Humans
  • Middle Aged
  • Risk Factors


  • Amyloid beta-Peptides
  • Apolipoprotein E4
  • Apolipoproteins E