SYNERGISTIC EFFECTS OF TRAUMATIC HEAD-INJURY AND APOLIPOPROTEIN-EPSILON-4 IN PATIENTS WITH ALZHEIMERS-DISEASE

The apolipoprotein-epsilon 4 allele increases the risk of Alzheimer's disease (AD), but cerebral deposition of beta-amyloid with age, a gene tic mutation, or head injury may contribute to the pathogenesis of thi s disease. We examined the risks of AD associated with traumatic head injury and apolipoprotein-epsilon 4 in 236 community-dwelling elderly persons. A 10-fold increase in the risk of AD was associated with both apolipoprotein-epsilon 4 and a history of traumatic head injury, comp ared with a two-fold increase in risk with apolipoprotein-epsilon 4 al one. Head injury in the absence of an apolipoprotein-epsilon 4 allele did not increase risk. These data imply that the biological effects of head injury may increase the risk of AD, but only through a synergist ic relationship with apolipoprotein-epsilon 4.