Cerebral amyloid-β accumulation and deposition following traumatic brain injury—A narrative review and meta-analysis of animal studies

Bird, Sabine; Sohrabi, Hamid R.; Sutton, T.A. A.; Weinborn, Michael; Rainey-Smith, Stephanie R.; Brown, Belinda M.; Patterson, Leigh; Taddei, Kevin; Gupta, Veer; Carruthers, Malcolm; Lenzo, Nat; Knuckey, Neville W.; Bucks, Romola S.; Verdile, Giuseppe; Martins, Ralph N.

doi:10.1016/j.neubiorev.2016.01.004

Cited by 39 publications

(28 citation statements)

References 97 publications

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“…Several human studies, however, have shown that APOE4 had no effect on outcome of TBI [12,49]. In contrast, the majority of animal studies, mostly in AD mouse models expressing human APP, have demonstrated APOE4 plays a significant role in determining the pathology and recovery following TBI, possibly in an age dependent manner [5,45,7]. The animal models of TBI obviously do not, and cannot, represent all aspects of brain pathology as a response to brain trauma at molecular, cellular and organ levels.…”

Section: Discussionmentioning

confidence: 99%

Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury

Castranio

Mounier

Wolfe

et al. 2017

Neurobiology of Disease

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Traumatic brain injury (TBI) is strongly linked to an increased risk of developing dementia, including chronic traumatic encephalopathy and possibly Alzheimer’s disease (AD). APOEε4 allele of human Apolipoprotein E (APOE) gene is the major genetic risk factor for late onset AD and has been associated with chronic traumatic encephalopathy and unfavorable outcome following TBI. To determine if there is an APOE isoform-specific response to TBI we performed controlled cortical impact on 3-month-old mice expressing human APOE3 or APOE4 isoforms. Following injury, we used several behavior paradigms to test for anxiety and learning and found that APOE3 and APOE4 targeted replacement mice demonstrate cognitive impairments following moderate TBI. Transcriptional profiling 14 days following injury revealed a significant effect of TBI, which was similar in both genotypes. Significantly upregulated by injury in both genotypes were mRNA expression and protein level of ABCA1 transporter and APOJ, but not APOE. To identify gene-networks correlated to injury and APOE isoform, we performed Weighted Gene Co-expression Network Analysis. We determined that the network mostly correlated to TBI in animals expressing both isoforms is immune response with major hub genes including Trem2, Tyrobp, Clec7a and Cd68. We also found a significant increase of TREM2, IBA-1 and GFAP protein levels in the brains of injured mice. We identified a network representing myelination that correlated significantly with APOE isoform in both injury groups. This network was significantly enriched in oligodendrocyte signature genes, such as Mbp and Plp1. Our results demonstrate unique and distinct gene networks at this acute time point for injury and APOE isoform, as well as a network driven by APOE isoform across TBI groups.

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Section: Discussionmentioning

confidence: 99%

Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury

Castranio

Mounier

Wolfe

et al. 2017

Neurobiology of Disease

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“…These processes promoted the clearance of macromolecular metabolites from the brain, during sleep ( 15 ). The disturbance of glymphatic transport due to inadequate sleep may mediate neuropathologies in AD, given that sleep disruption aggravates the assembly of Aβ plaques and tangles ( 119 , 120 ). Recent studies have focused on the effect of sleep deprivation on synaptic plasticity and on structural changes of brain regions related to learning and memory ( 121 , 122 ), and the progression of AD ( 123 – 125 ).…”

Section: The Importance Of Sleep In Diabetes-induced Dementiamentioning

confidence: 99%

The Glymphatic System in Diabetes-Induced Dementia

2018

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The glymphatic system has emerged as an important player in central nervous system (CNS) diseases, by regulating the vasculature impairment, effectively controlling the clearance of toxic peptides, modulating activity of astrocytes, and being involved in the circulation of neurotransmitters in the brain. Recently, several studies have indicated decreased activity of the glymphatic pathway under diabetes conditions such as in insulin resistance and hyperglycemia. Furthermore, diabetes leads to the disruption of the blood-brain barrier and decrease of apolipoprotein E (APOE) expression and the secretion of norepinephrine in the brain, involving the impairment of the glymphatic pathway and ultimately resulting in cognitive decline. Considering the increased prevalence of diabetes-induced dementia worldwide, the relationship between the glymphatic pathway and diabetes-induced dementia should be investigated and the mechanisms underlying their relationship should be discussed to promote the development of an effective therapeutic approach in the near future. Here, we have reviewed recent evidence for the relationship between glymphatic pathway dysfunction and diabetes. We highlight that the enhancement of the glymphatic system function during sleep may be beneficial to the attenuation of neuropathology in diabetes-induced dementia. Moreover, we suggest that improving glymphatic system activity may be a potential therapeutic strategy for the prevention of diabetes-induced dementia.

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“…Notably, this effect was seen after inhibition of cholinergic as well as adrenergic and serotonergic pathways in rats (through chemical lesions in the nucleus basalis of Meynert, the ascending noradrenergic bundle and the dorsal raphe nucleus, respectively). Formation of Aβ as one consequence of such APP induction has been widely confirmed in experimental traumatic brain injury (Bird et al, 2016). Related findings have been made in humans, where APP has been used as early marker of axonal damage after mechanical trauma (Sherriff et al, 1994).…”

Section: Amyloid and Tau Pathology Are Common In Many Cns Disordersmentioning

confidence: 86%

The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency

Sohre

Moosmann

2018

Preprint

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Alzheimer's disease is characterized by intracellular aggregates of hyperphosphorylated tau protein and extracellular plaques of amyloid β peptide, a product of APP processing. The origin of these pathological hallmarks has remained elusive. Here, we have tested the idea that both alterations, at the onset of the disease, may constitute compensatory responses to the same causative and initial trigger, namely NMDA receptor insufficiency. Treatment of rat cortical neurons with the specific NMDA receptor antagonist AP5 within 4 h caused a significant increase in tau phosphorylation at the AT8 and S404 epitopes as well as an increase in APP expression and Aβ40 secretion. Single intraperitoneal injections of the NMDA receptor open channel blocker MK-801 into wild-type mice reproduced all of these changes in a brain region-specific fashion either at latency 4 h or 24 h. Subchronic treatment with MK-801 for 6 weeks induced AT8, S404 and S396 immunoreactivity selectively in female mice. We conclude that the pivotal pathological alterations in Alzheimer's disease represent runaway physiological responses to persistently insufficient excitatory neurotransmission. In view of the evidence for excitatory insufficiency in trisomy 21 patients, PS1 mutation carriers and ApoE4 carriers, our data suggest a common pathomechanism behind familial, sporadic, and risk allele-triggered Alzheimer's disease. The potential of this mechanism to reconcile previous conflicting observations is discussed.

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Cerebral amyloid-β accumulation and deposition following traumatic brain injury—A narrative review and meta-analysis of animal studies

Cited by 39 publications

References 97 publications

Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury

Gene co-expression networks identify Trem2 and Tyrobp as major hubs in human APOE expressing mice following traumatic brain injury

The Glymphatic System in Diabetes-Induced Dementia

The pathological hallmarks of Alzheimer’s disease derive from compensatory responses to NMDA receptor insufficiency

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