Article

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: 31.43). 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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Available from: William Stewart, Sep 15, 2014
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    • "Traumatic brain injury (TBI) causes acute pathological changes in the brain which can lead to long-term neurodegeneration and an increased risk of developing Alzheimer's disease (AD) (reviewed in Johnson et al., 2010). A prominent pathological hallmark and proposed etiological agent of AD is the development of Aβ plaques (Hardy and Allsop, 1991). "
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    ABSTRACT: Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE,PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24hrs and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24hrs or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24hrs PI or 7d PI. There was a significant (p<0.001) increase in cross-sectional cortical area occupied by Iba-1 positive microglia in injured mice compared to sham animals, however this response did not differ between APP/PS1 and Wt mice (p>0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24hrs PI (compared to sites distant to the injury and the corresponding area in sham mice; p<0.01), but not after 7d PI (p>0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Mar 2015 · Experimental Neurology
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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). "

    Full-text · Dataset · Jan 2015
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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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    ABSTRACT: Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans.
    Full-text · Article · Jun 2014 · Alzheimer's and Dementia
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