Effect of APOE polymorphisms on early responses to traumatic brain injury

Jiang, Yong; Sun, Xiaochuan; Xia, Yuxian; Tang, Wenyuan; Cao, Yueqing; Gu, Yingjiang

doi:10.1016/j.neulet.2006.08.082

Cited by 43 publications

(32 citation statements)

References 31 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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IntroductionThe apolipoprotein E (APOE) ε4 allele associates with memory impairment in neurodegenerative diseases. Its association with memory after mild traumatic brain injury (mTBI) is unclear.Methods mTBI patients (Glasgow Coma Scale score 13–15, no neurosurgical intervention, extracranial Abbreviated Injury Scale score ≤1) aged ≥18 years with APOE genotyping results were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK‐TBI Pilot) study. Cohorts determined by APOE‐ε4(+/−) were assessed for associations with 6‐month verbal memory, measured by California Verbal Learning Test, Second Edition (CVLT‐II) subscales: Immediate Recall Trials 1–5 (IRT), Short‐Delay Free Recall (SDFR), Short‐Delay Cued Recall (SDCR), Long‐Delay Free Recall (LDFR), and Long‐Delay Cued Recall (LDCR). Multivariable regression controlled for demographic factors, seizure history, loss of consciousness, posttraumatic amnesia, and acute intracranial pathology on computed tomography (CT).ResultsIn 114 mTBI patients (APOE‐ε4(−)=79; APOE‐ε4(+)=35), ApoE‐ε4(+) was associated with long‐delay verbal memory deficits (LDFR: B = −1.17 points, 95% CI [−2.33, −0.01], p = .049; LDCR: B = −1.58 [−2.63, −0.52], p = .004), and a marginal decrease on SDCR (B = −1.02 [−2.05, 0.00], p = .050). CT pathology was the strongest predictor of decreased verbal memory (IRT: B = −8.49, SDFR: B = −2.50, SDCR: B = −1.85, LDFR: B = −2.61, LDCR: B = −2.60; p < .001). Seizure history was associated with decreased short‐term memory (SDFR: B = −1.32, p = .037; SDCR: B = −1.44, p = .038).ConclusionThe APOE‐ε4 allele may confer an increased risk of impairment of 6‐month verbal memory for patients suffering mTBI, with implications for heightened surveillance and targeted therapies. Acute intracranial pathology remains the driver of decreased verbal memory performance at 6 months after mTBI.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2017

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“…In humans, apoE is the major apolipoprotein expressed in the brain and exists as three isoforms, designated E2, E3, and E4. Many studies, including our previous clinical research, have demonstrated that the presence of the APOEe4 allele predisposes individuals to clinical deterioration in the acute phase and poor long-term outcome ( Jiang et al, 2006;Sorbi et al, 1995;Teasdale et al, 1997Teasdale et al, ,2005Zhou et al, 2008). Under normal physiologic conditions, apoE serves as an important mediator of cholesterol and lipid transport in the brain.…”

Section: Introductionmentioning

confidence: 99%

Administration of COG1410 Reduces Axonal Amyloid Precursor Protein Immunoreactivity and Microglial Activation after Controlled Cortical Impact in Mice

Jiang

Brody

2012

Journal of Neurotrauma

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Traumatic axonal injury (TAI) accounts for at least 35% of the morbidity and mortality in traumatic brain injury (TBI) patients without space-occupying lesions. It is also believed to be a key determinant of adverse outcomes such as cognitive dysfunction across the spectrum of TBI severity. Previous studies have shown that COG1410, a synthetic peptide derived from the apolipoprotein E (apoE) receptor binding region, has anti-inflammatory effects after experimental TBI, with improvements in cognitive recovery. However, the effects of COG1410 on axonal injury following TBI are not known. The current study evaluated the effects of 1 mg/kg daily COG1410 versus saline administered intravenously starting 30 min after controlled cortical impact (CCI) injury on pericontusional TAI in young, wild-type C57BL6/J male mice. We found that COG1410 did not affect the number of amyloid precursor protein (APP)-immunoreactive axonal varicosities in the pericontusional corpus callosum and external capsule at 24 h, but reduced APP-immunoreactive varicosities by 31% at 3 days ( p = 0.0023), and 36% at 7 days ( p = 0.0009). COG1410 significantly reduced the number of Iba1-positive cells with activated microglial morphology at all three time points by 21-30%. There was no effect of COG1410 on pericontusional white matter volume or silver staining at any time point. This indicates a possible effect of COG1410 on delayed but not immediate TAI. Future studies are needed to investigate the underlying mechanisms, therapeutic time window, and physiological implications of this effect.

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“…Moreover, excessively high [Ca 2+ ] i plays an important role in the apoptosis process after TBI. APOE polymorphism also influences the outcome of TBI, and our previous studies have already revealed that APOEe4 can deteriorate the outcome of patients at the early stage of TBI (Jiang et al, 2006(Jiang et al, , 2007(Jiang et al, , 2011, but the exact mechanism remains unclear. Furthermore, the relationship between APOE and [Ca 2+ ] i after mechanical injury has not been clarified.…”

Section: Discussionmentioning

confidence: 99%

Effects of ApoE on intracellular calcium levels and apoptosis of neurons after mechanical injury

et al. 2015

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Effect of APOE polymorphisms on early responses to traumatic brain injury

Cited by 43 publications

References 31 publications

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

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

Administration of COG1410 Reduces Axonal Amyloid Precursor Protein Immunoreactivity and Microglial Activation after Controlled Cortical Impact in Mice

Effects of ApoE on intracellular calcium levels and apoptosis of neurons after mechanical injury

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