Evaluating the Effects of APOE 4 after Mild Traumatic Brain Injury in Experimental Models

Excerpt

The best known genetic risk factor for poor outcome after traumatic brain injury (TBI) in adults is the E4 allele of the apolipoprotein E (APOE) gene. Studying the effect of APOE alleles on outcome after mild TBI (mTBI) has proven challenging in clinical studies, due to many factors including heterogeneity of injuries, confounding clinical factors such as age and unmeasured associated genotypes, and general expense of large-scale studies. Studying the effect of APOE on outcome after mTBI in experimental models may overcome many of these hurdles, but a thorough understanding of injury and APOE models is needed prior to undertaking such studies.

Mild traumatic brain injury is a common injury, with more than 3.8 million new cases annually just in the United States alone. mTBI is the most common form of TBI, with nearly 75% of all TBI being characterized as mild. However, despite the characterization as “mild,” mTBI can have long-term and devastating effects. Recently, there has been increased interest in studying short- and long-term effects of mTBI, especially in military and athletic populations.

In studying mTBI, clinicians have observed that outcomes may differ markedly, even among patients with similar mechanisms of injury. These observations have led to the search for genetic risk factors potentially associated with worse outcome after TBI (Nicoll, 1996). The best known genetic risk factor associated with poor outcome after TBI in adults is the E4 allele of the apolipoprotein E (APOE) gene (Jordan et al., 1997; Teasdale et al., 1997).

Studying the effect of APOE on outcome after mTBI has proven challenging in clinical studies because of many factors including heterogeneity of injuries, confounding clinical factors such as age and unmeasured associated genotypes, and general expense of large-scale studies. Studying the effect of APOE on outcome after mTBI in experimental models may overcome many of these hurdles, but a thorough understanding of injury and APOE models is needed before undertaking such studies. The purpose of this chapter is to review experimental models of APOE and mTBI, starting with the clinical literature that has informed the experimental modeling.