Apolipoprotein E-ε4 genotype predicts a poor outcome in survivors of traumatic brain injury

Abstract

The results demonstrate a strong association between the APOE-epsilon4 allele and a poor clinical outcome, implying genetic susceptibility to the effect of brain injury. Additional studies of TBI patients are warranted to confirm their findings.

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).…”

Apolipoprotein E epsilon 4 (APOE‐ε4) genotype is associated with decreased 6‐month verbal memory performance after mild traumatic brain injury

“…Our analysis replicates this phenomenon, as CT pathology was the driver of decreased cognitive performance following mTBI, with greater deleterious associations with consolidation and retrieval rather than encoding. This supports the idea that following ischemia and neuronal damage, the reduced antioxidant and biological activity of the ε 4 allele may exacerbate vascular endothelial injury (Bell et al., 2012; Halliday et al., 2016) and lead to cognitive deficits (Friedman et al., 1999). Similar results have been described in AD patients with left temporal and/or hippocampal damage, where a subtle decline in episodic memory occurs prior to the emergence of full dementia.…”

“…ApoE is a key regulator of plasma lipid levels produced in abundance in the brain along with ApoE receptors in order to mediate synaptic repair, remodeling, and protection (Blackman, Worley, & Strittmatter, 2005; Ignatius et al., 1986; Nathan et al., 1994). The gene for ApoE is located on chromosome 19 and is highly polymorphic (Friedman et al., 1999). Differences in the tertiary structure and in the charge distribution of the APOE isoforms determine the capacity for cholesterol homeostasis through binding to receptors, to other proteins, and through intracellular trafficking pathways and second messengers (Strittmatter & Bova Hill, 2002; Saito et al., 2003).…”

“…This could be due to increased expression of APOE in astrocytes following ischemic brain injury and neuronal degeneration (Friedman et al., 1999), furthered by the association between APOE‐ ε 4 and increased oxidative stress (Jiang et al., 2006). In a landmark study of 984 patients by Teasdale et al.…”

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

“…Although this finding has generated fewer biological insights than has the identification, through pedigree studies, of genes implicated in rare, mendelian forms of Alzheimer disease 78 , it has transformed epidemiological and clinical investigation of dementia and related phenotypes. Consequently, it is now known that ApoE4 is associated with the age of onset of Alzheimer disease 95 , the process of cognitive decline in 'normal' aging 96 , altered magnetic resonance imaging findings in asymptomatic individuals 97,98 , risk of chronic traumatic brain injury in boxers 99 and clinical outcome in survivors of traumatic brain injury 100 .…”