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Traumatic brain injury and amyloid-β pathology: a link to Alzheimer’s disease? Nat Rev Neurosci

University of Glasgow, University Avenue, Glasgow G12 8QQ, UK.
Nature Reviews Neuroscience (Impact Factor: 31.38). 03/2010; 11(5):361-70. DOI: 10.1038/nrn2808
Source: PubMed

ABSTRACT Traumatic brain injury (TBI) has devastating acute effects and in many cases seems to initiate long-term neurodegeneration. Indeed, an epidemiological association between TBI and the development of Alzheimer's disease (AD) later in life has been demonstrated, and it has been shown that amyloid-β (Aβ) plaques — one of the hallmarks of AD — may be found in patients within hours following TBI. Here, we explore the mechanistic underpinnings of the link between TBI and AD, focusing on the hypothesis that rapid Aβ plaque formation may result from the accumulation of amyloid precursor protein in damaged axons and a disturbed balance between Aβ genesis and catabolism following TBI.

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    • "Characteristic features of AD are the formation of β-amyloid (Aβ) plaques, neurofi brillary tangles and the loss of connections between neurons. AD and TBI share several common gene expression changes such as amyloid precursor proteins (APP), BACE1, ApoE4 and tau (Johnson et al., 2010; Liliang et al., 2010a,b; Sivanandam and Thakur, 2012). Post mortem analyses of severe TBI patients showed Aβ deposits in the cortical area of the brain in about 30% of patients (Roberts et al., 1994). "
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    • "Diffuse injuries include hypoxia/ischemia, vascular damage, and diffuse macro-/ microstructural axonal injury. Numerous epidemiologic studies have linked TBI to AD (reviewed in [6] [7] [8] [9] [10] [11] [12]). A history of TBI may be associated with earlier onset of AD [1,6,7,13–16] and the apolipoprotein E ε4 (APOE ε4) allele may worsen outcome [13,17–28]. "
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    • "After a traumatic brain injury, there is an acute phase of calcium dyshomeostasis due to cellular responses to injury which includes glutamatergic excitotoxicity and lasts minutes to hours. Subsequently, there is often a sustained pattern of calcium dysregulation that includes ER mechanisms and can last days to weeks, and is associated with amyloid accumulation, tau pathology, cell death, and cognitive deficits (Deshpande et al., 2008; Johnson et al., 2010; Shively et al., 2012; Weber, 2004, 2012). This pattern of degenerative pathology and memory impairment is not dissimilar to that observed in clinical AD and in AD mouse models, thus serving as a potential common factor driving the increased incidence of aggressive dementia in traumatic brain injury patients. "
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