Apolipoprotein E Epsilon 4 Genotype, Mild Traumatic Brain Injury, and the Development of Chronic Traumatic Encephalopathy.

Hansen Deng,Pavan S Upadhyayula,Troy Lam,Nebil Mohammed,John K Yue,Catherine G Suen,Angel Ordaz,Eva M Gillis-Buck,Caroline G Melhado

doi:10.3390/medsci6030078

Abstract

The annual incidence of mild traumatic brain injury (MTBI) is 3.8 million in the USA with 10–15% experiencing persistent morbidity beyond one year. Chronic traumatic encephalopathy (CTE), a neurodegenerative disease characterized by accumulation of hyperphosphorylated tau, can occur with repetitive MTBI. Risk factors for CTE are challenging to identify because injury mechanisms of MTBI are heterogeneous, clinical manifestations and management vary, and CTE is a postmortem diagnosis, making prospective studies difficult. There is growing interest in the genetic influence on head trauma and development of CTE. Apolipoprotein epsilon 4 (APOE-ε4) associates with many neurologic diseases, and consensus on the ε4 allele as a risk factor is lacking. This review investigates the influence of APOE-ε4 on MTBI and CTE. A comprehensive PubMed literature search (1966 to 12 June 2018) identified 24 unique reports on the topic (19 MTBI studies: 8 athletic, 5 military, 6 population-based; 5 CTE studies: 4 athletic and military, 1 leucotomy group). APOE-ε4 genotype is found to associate with outcomes in 4/8 athletic reports, 3/5 military reports, and 5/6 population-based reports following MTBI. Evidence on the association between APOE-ε4 and CTE from case series is equivocal. Refining modalities to aid CTE diagnosis in larger samples is needed in MTBI.

Highlights

Mild traumatic brain injury (MTBI) accounts for 70–90% of all traumatic brain injury (TBI), with an estimated 10–15% of mild traumatic brain injury (MTBI) patients reporting persistent cognitive and/or neuropsychiatric deficits at one year post-injury and beyond [1,2,3]
While four studies did not note an association between APOE-ε4 carriers and MTBI outcomes, four others reported otherwise
2008, a prospective cohort of 318 various collegiate athletes (25% possessing APOE-ε4 allele), recorded 28 athletes experiencing concussions, with no association demonstrated between concussion incidence and ε4 [39]

Summary

Introduction

Mild traumatic brain injury (MTBI) accounts for 70–90% of all traumatic brain injury (TBI), with an estimated 10–15% of MTBI patients reporting persistent cognitive and/or neuropsychiatric deficits at one year post-injury and beyond [1,2,3]. Of particular interest are patients subject to. 2018, 6, x FOR PEER REVIEW repetitive head traumaorincontact the military contact sports, contributing to the risk of chronic traumatic trauma in the military sports,orcontributing to the risk of chronic traumatic encephalopathy encephalopathy (CTE).

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Conclusion