Widespread τ and amyloid-β pathology many years after a single traumatic brain injury in humans

Brain Pathol. 2012 Mar;22(2):142-9. doi: 10.1111/j.1750-3639.2011.00513.x. Epub 2011 Sep 12.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / adverse effects*
  • Brain Damage, Chronic / metabolism
  • Brain Damage, Chronic / pathology*
  • Brain Damage, Chronic / physiopathology
  • Brain Injuries / metabolism
  • Brain Injuries / pathology*
  • Brain Injuries / physiopathology
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neurofibrillary Tangles / pathology*
  • Plaque, Amyloid / pathology*
  • Young Adult
  • tau Proteins / adverse effects*


  • Amyloid beta-Peptides
  • tau Proteins