Evidence from experimental and clinical traumatic brain injury studies has confirmed the important role that APOE plays in the inflammatory response and neuronal repair mechanisms following traumatic brain injury. Sporadic clinical reports have supported the association between APOE e4 status and human traumatic brain injury outcome. Currently, there are many unanswered questions. Is the effect of APOE
4 on traumatic brain injury outcome confined to white or white derived population groups only? It is presently unknown whether APOE polymorphism is consistent in modifying the genetic response to traumatic brain injury in all major racial groups and in different geographical regions. Given the high interpopulation and regional variation, together with the genetic susceptibility of the APOE
4 allele to contemporary environmental factors, further clinical studies are warranted. In addition, it is unknown presently how observations recorded in transgenic animal models will translate to human conditions.
How does the APOE
4 allele influence traumatic brain injury severity, or the type of injury—diffuse versus focal? What is the effect of APOE
4 on sex based human traumatic brain injury outcome? Is this effect confined to adults only or does it apply to a developing brain also, and what is the influence of APOE
4 status on injury to other parts of the neuraxis, such as the spinal cord?
“It is presently unknown whether APOE polymorphism is consistent in modifying the genetic response to traumatic brain injury in all major racial groups and in different geographical regions”
Another alarming facet of APOE status is that the prognostication of traumatic brain injury outcome may have serious medicolegal and financial ramifications for patients and their families. It may be possible in the future that patients are biased by insurance companies according to their expression of genetic and molecular markers. In addition, insurance companies may preclude an individual on the basis of his or her APOE
4 status from pursuing certain high risk sports or occupations where the potential for traumatic brain injury is greater. The ramifications of APOE
4 status may assume a whole new dimension with “genetic stereotyping” taking on greater importance in the future.
Take home messages
- Apolipoprotein E (APOE) 4 has been shown to contribute to the development of Alzheimer’s disease, although there appear to be racial and geographical variations, and this may not be true for African populations
- This variation may the result of Western environmental conditions, such as diet and longer life spans
- APOE 4 and traumatic brain injury appear to act synergistically in the development of Alzheimer’s disease
- APOE 4 is associated with a poor outcome in traumatic brain injury, but again there may be racial and geographical variations
- The mechanisms underlying these effects are unclear but the amyloid β protein is thought to be involved
- More research into APOE 4 and traumatic brain injury is needed