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Association of APOE e4 and cerebrovascular pathology in traumatic brain injury
  1. C Smith1,2,
  2. D I Graham1,
  3. L S Murray3,
  4. J Stewart1,
  5. J A R Nicoll1,4
  1. 1Department of Neuropathology, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, Glasgow UK
  2. 2Neuropathology Laboratory, Department of Pathology, University of Edinburgh, Western General Hospital, Edinburgh, UK
  3. 3Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, UK
  4. 4Division of Clinical Neurosciences, University of Southampton, Southampton General Hospital, Southampton, UK
  1. Correspondence to:
 Dr C Smith
 Neuropathology Laboratory, Department of Pathology, University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK; col.smith{at}


Background: Previous studies have found the e4 allele of the apolipoprotein E gene (APOE e4) is associated with an unfavourable outcome after head injury, but this has not been related to specific pathological features.

Objectives: This study tested the postulate that head injured patients with APOE e4, amounting to approximately a third of the population, are selectively predisposed to one or more of the different pathological features that constitute the response to traumatic brain injury (TBI), and that this underlies the association of APOE e4 with poor clinical outcome.

Methods: Included in the study were 239 fatal cases of TBI (1987–1999) for which APOE genotypes were determined from archival tissue. For each case, specific pathological features of trauma were recorded by researchers blinded to the APOE e4 status. Of the 239 cases examined, 83 (35%) were APOE e4 carriers and 156 (65%) were non-carriers.

Results: Possession of APOE e4 was associated with a greater incidence of moderate or severe contusions (42% v 30% for carriers versus e4 non-carriers; p =  0.05) and there was a trend towards a greater incidence of severe ischaemic brain damage (54% v 42%; p =  0.08). Significant differences were not noted between the other pathological features examined.

Conclusions: Possession of APOE e4 is associated with a greater incidence of moderate/severe contusional injury and severe ischaemic brain damage in fatal cases of TBI. This may be relevant to the relatively poor outcome from traumatic brain injury in patients with APOE e4 identified in clinical studies.

  • APP, beta-amyloid precursor protein
  • DAI, diffuse axonal injury
  • TAI, traumatic axonal injury
  • TBI, traumatic brain injury
  • TCI, total contusion index
  • APOE
  • polymorphisms
  • head injury
  • contusions
  • ischaemic damage

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  • Competing interests: none

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