The Association Between Apolipoprotein E and Functional Outcome After Traumatic Brain Injury

Li, Lizhuo; Bao, Yijun; He, Songbai; Wang, Gang; Guan, Yanlei; Ma, Dongjie; Wu, Rongting; Wang, Pengfei; Huang, Xiaolong; Tao, Shanwei; Liu, Qiwen; Wang, Yunjie; Yang, Jingyun

doi:10.1097/md.0000000000002028

Cited by 44 publications

(27 citation statements)

References 43 publications

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“…However, patients within these studies with long expansions of Rep1 showed increased risk of PD (ORs 3–5×) 26. Similar relationships exist for other genetic factors: Apolipoprotein E (APOE) status is linked to adverse outcomes after TBI,27 s22 and when combined into polygenic risk scores may predict significant amounts of variability in neurodegenerative outcomes after TBI. s23…”

Section: How Common Is Dementia After Head Injury?mentioning

confidence: 71%

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Graham

Sharp

2019

J Neurol Neurosurg Psychiatry

226

160

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Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer’s disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss.

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Section: How Common Is Dementia After Head Injury?mentioning

confidence: 71%

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Graham

Sharp

2019

J Neurol Neurosurg Psychiatry

226

160

View full text Add to dashboard Cite

show abstract

“…A longstanding concern with many clinical studies is reliance on self-report and use of diagnostic verbiage in medical records to identify a correlation between TBI and post-injury development of AD ( 32 ). Also, several clinical studies report that individuals with genetic predisposition to developing AD (ApoE4 risk alleles) display altered outcome after TBI making the distinction between environmental and genetic risk factors for post-injury recovery unclear ( 33 , 34 ). Despite preclinical studies providing evidence for successful pharmacologic intervention, more than 30 phase-III clinical trials have failed to improve secondary injury outcome measures after TBI ( 35 – 37 ).…”

Section: Introduction To Traumatic Brain Injury (Tbi) and Alzheimer’smentioning

confidence: 99%

The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease

2018

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The post-injury inflammatory response is a key mediator in long-term recovery from traumatic brain injury (TBI). Moreover, the immune response to TBI, mediated by microglia and macrophages, is influenced by existing brain pathology and by secondary immune challenges. For example, recent evidence shows that the presence of beta-amyloid and phosphorylated tau protein, two hallmark features of AD that increase during normal aging, substantially alter the macrophage response to TBI. Additional data demonstrate that post-injury microglia are “primed” and become hyper-reactive following a subsequent acute immune challenge thereby worsening recovery. These alterations may increase the incidence of neuropsychiatric complications after TBI and may also increase the frequency of neurodegenerative pathology. Therefore, the purpose of this review is to summarize experimental studies examining the relationship between TBI and development of AD-like pathology with an emphasis on the acute and chronic microglial and macrophage response following injury. Furthermore, studies will be highlighted that examine the degree to which beta-amyloid and tau accumulation as well as pre- and post-injury immune stressors influence outcome after TBI. Collectively, the studies described in this review suggest that the brain’s immune response to injury is a key mediator in recovery, and if compromised by previous, coincident, or subsequent immune stressors, post-injury pathology and behavioral recovery will be altered.

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“…Another meta-analysis of six studies including a total of 358 cases of pediatric TBI revealed that at 6 months, there was over two-times higher odds of poor outcome following TBI in children with at least one APOE-ϵ4 allele, compared with children without ϵ4 allele [ 33 ]. In a meta-analysis of 12 studies on Apo E and functional outcome after TBI revealed an association with increased risk of unfavorable long-term functional outcome (≥6 months) [ 34 ].…”

Section: Macromolecular Components Of the Neurometabolic Cascadementioning

confidence: 99%

Genetic findings in sport-related concussions: potential for individualized medicine?

McDevitt

Krynetskiy

2017

Concussion

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Concussion is a traumatic transient disturbance of the brain. In sport, the initial time and severity of concussion is known giving an opportunity for subsequent analysis. Variability in susceptibility and recovery between individual athletes depends, among other parameters, on genetic factors. The genes-encoding polypeptides that determine incidence, severity and prognosis for concussion are the primary candidates for genetic analysis. Genetic polymorphisms in the genes contributing to plasticity and repair (APOE), synaptic connectivity (GRIN2A), calcium influx (CACNA1E), uptake and deposit of glutamate (SLC17A7) are potential biomarkers of concussion incidence and recovery rate. With catalogued genetic variants, prospective genotyping of athletes at the beginning of their career will allow medical professionals to improve concussion management and return-to-play decisions.

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The Association Between Apolipoprotein E and Functional Outcome After Traumatic Brain Injury

Abstract: Supplemental Digital Content is available in the text

Cited by 44 publications

References 43 publications

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

Understanding neurodegeneration after traumatic brain injury: from mechanisms to clinical trials in dementia

The Inflammatory Continuum of Traumatic Brain Injury and Alzheimer’s Disease

Genetic findings in sport-related concussions: potential for individualized medicine?

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