title: Widespread τ and amyloid-β pathology many years after a single traumatic brain injury in humans.
abstract: While a history of a single traumatic brain injury (TBI) is associated with the later development of syndromes of cognitive impairment such as Alzheimer's disease, the long-term pathology evolving after single TBI is poorly understood. However, a progressive tauopathy, chronic traumatic encephalopathy, is described in selected cohorts with a history of repetitive concussive/mild head injury. Here, post-mortem brains from long-term survivors of just a single TBI (1-47 years survival; n=39) vs. uninjured, age-matched controls (n=47) were examined for neurofibrillary tangles (NFTs) and amyloid-β (Aβ) plaques using immunohistochemistry and thioflavine-S staining. Detailed maps of findings permitted classification of pathology using semiquantitative scoring systems. NFTs were exceptionally rare in young, uninjured controls, yet were abundant and widely distributed in approximately one-third of TBI cases. In addition, Aβ-plaques were found in a greater density following TBI vs. controls. Moreover, thioflavine-S staining revealed that while all plaque-positive control cases displayed predominantly diffuse plaques, 64% of plaque-positive TBI cases displayed predominantly thioflavine-S-positive plaques or a mixed thioflavine-S-positive/diffuse pattern. These data demonstrate that widespread NFT and Aβ plaque pathologies are present in up to a third of patients following survival of a year or more from a single TBI. This suggests that a single TBI induces long-term neuropathological changes akin to those found in neurodegenerative disease.
authors.affiliation: Penn Center for Brain Injury and Repair and Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Victoria E
authors.initials: VE
authors.lastname: Johnson
authors.forename: William
authors.initials: W
authors.lastname: Stewart
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000009:adverse effects*; D001925:Brain Damage, Chronic / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology*; D058225:Plaque, Amyloid / Q000473:pathology*; D055815:Young Adult; D016875:tau Proteins / Q000009:adverse effects*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins