Apolipoprotein E epsilon4 associated with chronic traumatic brain injury in boxing

JAMA. 1997 Jul 9;278(2):136-40.


Context: Given the similarities between Alzheimer disease and dementia pugilistica, we evaluated the relationship between apolipoprotein E (APOE) genotype and chronic traumatic brain injury (CTBI) in boxers to determine whether there is a genetic susceptibility to the effects of head trauma.

Objective: To assess the relationship between CTBI and APOE genotype in boxers.

Design and setting: Clinical characterization of 24 volunteer and 6 referred boxers in an outpatient setting.

Participants: Thirty professional boxers aged 23 to 76 years underwent neurologic and behavioral assessment in conjunction with APOE genotyping.

Main outcome measures: Apolipoprotein E genotype was examined in relationship to measures of CTBI. A 10-point clinical rating scale (0-9), the Chronic Brain Injury (CBI) scale, was devised to assess the severity of traumatic encephalopathy associated with boxing. Boxers with abnormal CTBI scores were further classified on the basis of whether their impairments were possibly or probably related to boxing. Scores were analyzed in relation to boxing exposure (number of bouts) and APOE genotype.

Results: Among the 30 boxers, 11 were found to be normal (CBI score=0), 12 showed mild deficits (CBI score=1-2), 4 were moderately impaired (CBI score=3-4), and 3 showed signs of severe impairment (CBI score > 4). High-exposure boxers (ie, those with > or = 12 professional bouts) had significantly higher CBI scores (mean [SD], 2.6 [1.9]) than low-exposure boxers (mean [SD], 0.3 [0.7]) (P<.001), indicating that neurologic impairment as measured by the CBI scale seems related to boxing exposure. The APOE genotype frequencies of the study population were approximately the same as those found in the general population. Boxers with low exposure had mean CBI scores of 0.33, irrespective of APOE genotype. However, high-exposure boxers with an APOE epsilon4 allele had significantly greater CBI scores (mean [SD], 3.9 [2.3]) than high-exposure boxers without APOE epsilon4 (mean [SD], 1.8 [1.2]) (P=.04). All boxers with severe impairment possessed at least 1 APOE epsilon4 allele. The tendency for greater CTBI among those with both high exposure and an epsilon4 allele was statistically significant at the P<.001 level.

Conclusions: These preliminary findings suggest that possession of an APOE epsilon4 allele may be associated with increased severity of chronic neurologic deficits in high-exposure boxers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Apolipoproteins E / metabolism
  • Boxing / injuries*
  • Brain Injuries / etiology
  • Brain Injuries / metabolism*
  • Brain Injuries / physiopathology
  • Gene Frequency
  • Genotype
  • Heterozygote
  • Humans
  • Middle Aged
  • Neuropsychological Tests
  • Risk Factors
  • Statistics, Nonparametric
  • Trauma Severity Indices


  • Apolipoprotein E4
  • Apolipoproteins E