Synergistic Effects of Traumatic Head Injury and Apolipoprotein-epsilon4 in Patients With Alzheimer's Disease

Abstract

The apolipoprotein-epsilon 4 allele increases the risk of Alzheimer's disease (AD), but cerebral deposition of beta-amyloid with age, a genetic mutation, or head injury may contribute to the pathogenesis of this 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, compared with a two-fold increase in risk with apolipoprotein-epsilon 4 alone. 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 synergistic relationship with apolipoprotein-epsilon 4.

Increased Anticholinergic Challenge-Induced Memory Impairment Associated with the APOE-ɛ4 Allele in the Elderly: A Controlled Pilot Study

“…More specifically, the benzodiazepine effect that differentiated between the e4 and the non-e4 groups was seen on measures of long-term memory 5 h after the treatment was administered. Thus, the decreased recovery that we observed in the e4 participants following acute administration of two classes of treatments with relatively distinct pharmacological actions is consistent with other findings and suggest that the e4 allele is associated with a general vulnerability of the brain to recover from various pharmacological and neurological insults (Alberts et al, 1995;Friedman et al, 1999;Mayeux et al, 1996;Sorbi et al, 1995).…”

Gene–environment correlations: a review of the evidence and implications for prevention of mental illness

“…95 Typically, however, researchers utilizing the case-control design have used log-linear analyses to test for G Â E effects on, for example, Alzheimer's Disease (e.g., Jarvik et al, 96 Mayeaux et al 97 ), suggesting that the results may be biased by any non-independence of genetic and environmental risk factors.…”

Mind the gaps—advancing research into short-term and long-term neuropsychological outcomes of youth sports-related concussions

“…90,91 Studies suggest an interaction between APOE ε4 and sex, such that APOE ε4-related risk of AD is more prominent in women than in men. 92,93 The APOE genotype acts synergistically with TBI in increasing the risk of AD, 94 although its hypothesized risk association with CTE as an outcome of repetitive mTBI requires more study. 95 No consensus has yet been reached on the effects of APOE isotype on the outcome of paediatric TBI, but data from adults suggest that APOE ε4 negatively influences concussion outcomes.…”