Traumatic brain injury and amyloid-β pathology: a link to Alzheimer's disease?

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.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Traumatic brain injury (TBI) is a major health issue comprising a heterogeneous and complex array of pathologies. Over the last several decades, numerous animal models have been developed to address the diverse nature of human TBI. The clinical relevance of these models has been a major point of reflection given the poor translation of pharmacologic TBI interventions to the clinic. While previously characterized broadly as either focal or diffuse, this classification is falling out of favor with increased awareness of the overlap in pathologic outcomes between models and an emerging consensus that no one model is sufficient. Moreover, an appreciation of injury biomechanics is essential in recapitulating and interpreting the spectrum of TBI neuropathology observed in various established models of dynamic closed-head TBI. While these models have replicated many specific features of human TBI, an enhanced context with clinical relevancy will facilitate the further elucidation of the mechanisms and treatment of injury. © 2015 Elsevier B.V. All rights reserved.
    Handbook of Clinical Neurology 01/2015; 127:115-28. DOI:10.1016/B978-0-444-52892-6.00008-8
  • [Show abstract] [Hide abstract]
    ABSTRACT: Traumatic brain injury, a leading cause of mortality and morbidity, is divided into three grades of severity: mild, moderate, and severe, based on the Glasgow Coma Scale, the loss of consciousness, and the development of post-traumatic amnesia. Although mild traumatic brain injury, including concussion and subconcussion, is by far the most common, it is also the most difficult to diagnose and the least well understood. Proper recognition, management, and treatment of acute concussion and mild traumatic brain injury are the fundamentals of an emerging clinical discipline. It is also becoming increasingly clear that some mild traumatic brain injuries have persistent, and sometimes progressive, long-term debilitating effects. Evidence indicates that a single traumatic brain injury can precipitate or accelerate multiple age-related neurodegenerations, increase the risk of developing Alzheimer's disease, Parkinson's disease, and motor neuron disease, and that repetitive mild traumatic brain injuries can provoke the development of a tauopathy, chronic traumatic encephalopathy. Clinically, chronic traumatic encephalopathy is associated with behavioral changes, executive dysfunction, memory loss, and cognitive impairments that begin insidiously and progress slowly over decades. Pathologically, chronic traumatic encephalopathy produces atrophy of the frontal and temporal lobes, thalamus, and hypothalamus, septal abnormalities, and abnormal deposits of hyperphosphorylated tau (τ) as neurofibrillary tangles and disordered neurites throughout the brain. The incidence and prevalence of chronic traumatic encephalopathy and the genetic risk factors critical to its development are currently unknown. Chronic traumatic encephalopathy frequently occurs as a sole diagnosis, but may be associated with other neurodegenerative disorders, including Alzheimer's disease, Lewy body disease, and motor neuron disease. Currently, chronic traumatic encephalopathy can be diagnosed only at autopsy; however, promising efforts to develop imaging, spinal fluid, and peripheral blood biomarkers are underway to diagnose and monitor the course of disease in living subjects. © 2015 Elsevier B.V. All rights reserved.
    Handbook of Clinical Neurology 01/2015; 127:45-66. DOI:10.1016/B978-0-444-52892-6.00004-0
  • Source

Full-text (2 Sources)

Available from
Sep 15, 2014