title: Post-traumatic neurodegeneration and chronic traumatic encephalopathy.
abstract: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity around the world. Concussive and subconcussive forms of closed-head injury due to impact or blast neurotrauma represent the most common types of TBI in civilian and military settings. It is becoming increasingly evident that TBI can lead to persistent, long-term debilitating effects, and in some cases, progressive neurodegeneration and chronic traumatic encephalopathy (CTE). The epidemiological literature suggests that a single moderate-to-severe TBI may be associated with accelerated neurodegeneration and increased risk of Alzheimer's disease, Parkinson's disease, or motor neuron disease. However, the pathologic phenotype of these post-traumatic neurodegenerations is largely unknown and there may be pathobiological differences between post-traumatic disease and the corresponding sporadic disorder. By contrast, the pathology of CTE is increasingly well known and is characterized by a distinctive pattern of progressive brain atrophy and accumulation of hyperphosphorylated tau neurofibrillary and glial tangles, dystrophic neurites, 43 kDa TAR DNA-binding protein (TDP-43) neuronal and glial aggregates, microvasculopathy, myelinated axonopathy, neuroinflammation, and white matter degeneration. Clinically, CTE is associated with behavioral changes, executive dysfunction, memory deficits, and cognitive impairments that begin insidiously and most often progress slowly over decades. Although research on the long-term effects of TBI is advancing quickly, the incidence and prevalence of post-traumatic neurodegeneration and CTE are unknown. Critical knowledge gaps include elucidation of pathogenic mechanisms, identification of genetic risk factors, and clarification of relevant variables-including age at exposure to trauma, history of prior and subsequent head trauma, substance use, gender, stress, and comorbidities-all of which may contribute to risk profiles and the development of post-traumatic neurodegeneration and CTE. This article is part of a Special Issue entitled 'Traumatic Brain Injury'.
authors.affiliation: Boston University Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Daneshvar
authors.affiliation: Boston University Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Pharmacology & Experimental Therapeutics, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Neurosurgery, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Photonics Center, Boston University, 1 Silber Way, Boston, MA 02115, USA; Department of Biomedical Engineering, Boston University, 1 Silber Way, Boston, MA 02115, USA; Department of Electrical and Computer Engineering, Boston University, 1 Silber Way, Boston, MA 02115, USA; Department of Mechanical Engineering, Boston University, 1 Silber Way, Boston, MA 02115, USA.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Goldstein
authors.affiliation: Boston University Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA.
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Kiernan
authors.affiliation: Boston University Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; VA Boston Healthcare System, 150 South Huntington Avenue, Jamaica Plain, MA 02130, USA.
authors.forename: Thor D
authors.initials: TD
authors.lastname: Stein
authors.affiliation: Boston University Chronic Traumatic Encephalopathy Program, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Boston University Alzheimer's Disease Center, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Neurology, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, 72 E. Concord St., Boston, MA 02118, USA; VA Boston Healthcare System, 150 South Huntington Avenue, Jamaica Plain, MA 02130, USA.
authors.forename: Ann C
authors.initials: AC
authors.lastname: McKee
mesh_terms: D000818:Animals; D001519:Behavior / Q000502:physiology*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D020208:Brain Injury, Chronic / Q000378:metabolism* / Q000503:physiopathology; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins
keywords: Axonal injury; Blast and impact neurotrauma; Brain trauma; Chronic traumatic encephalopathy; Concussion; Motor neuron disease; Posttraumatic neurodegeneration; Tau protein; Traumatic brain injury