Effects of closed traumatic brain injury and genetic factors on the development of Alzheimer's disease

Eur J Neurol. 2001 Nov;8(6):707-10. doi: 10.1046/j.1468-1331.2001.00322.x.


In order to assess the impact of traumatic brain injury (TBI) and Apolipoprotein E (ApoE) allele frequency on the development of Alzheimer's disease (AD), we examined: (i) the incidence of AD pathology in 55 consecutive autopsy cases (mean age +/- SD 77.6 +/- 7.3 years) with residual closed TBI lesions and (ii) the frequency of TBI residuals in 53 age-matched autopsy proven AD cases. In both series, ApoE was evaluated from archival paraffin-embedded brain material. The results were as follows: (i) In the TBI series, 12.7% showed Consortium to Establish a Registry for Alzheimer's disease (CERAD) definite and 9.1% probable AD, only one with ApoEepsilon4. From the remaining 43 non-AD cases, three had ApoEepsilon4. The prevalence of 21.8% AD in this small autopsy cohort was significantly higher than 3.3% in a recent large clinical series and 14% in the general population over the age of 70. (ii) In the AD cohort with ApoEepsilon4 allele frequency of 30% similar to other AD series, residuals of TBI were seen in 4 brains (7.5%), all lacking the ApoEepsilon4 allele. TBI incidence was slightly higher than 8.5% in the clinical MIRAGE study. The results of this first retrospective autopsy study of TBI, ApoE allele frequency, and AD confirms clinical studies suggesting severe TBI to be a risk factor for the development of AD particularly in subjects lacking ApoEepsilon4.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / epidemiology*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology
  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E / genetics
  • Brain Injuries / epidemiology*
  • Brain Injuries / genetics*
  • Brain Injuries / pathology
  • Cohort Studies
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Retrospective Studies


  • Apolipoprotein E3
  • Apolipoprotein E4
  • Apolipoproteins E