Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans
Open accessAbstract
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.
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Sustaining even a single traumatic brain injury can result in progressive neurofibrillary tangle formation that is more extensive and severe than what is expected with normal aging.
“For instance, sustaining even a single TBI can result in progressive NFT formation that is more extensive and severe than what is expected with normal aging (Johnson et al., 2012; Zanier et al., 2018).”
From Tauopathy and Epilepsy Comorbidities and Underlying Mechanisms (2022) · cites this paper as Johnson et al., 2012
Other studies indicate that neuroinflammation, b-amyloid deposition, and accumulation of TDP-43 and p-tau can arise following a single moderate-severe TBI, and there is emerging evidence that multiple types of neuropathology can be present following repetitive mild TBI.
“There are other studies, however, indicating that different types of neuropathology, such as neuroinflammation (36), b-amyloid deposition (37), and accumulation of TDP-43 (38) and p-tau (37, 39, 40) can and do arise following a single moderate-severe TBI (41)(42)(43), and there is emerging evidence that multiple types of neuropathology can be present following repetitive mild TBI (43,44).”
From Mild Chronic Traumatic Encephalopathy Neuropathology in People With No Known Participation in Contact Sports or History of Repetitive Neurotrauma (2019) · cites this paper as [37]
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- Authors
- Johnson, V. E., Stewart, W., & Smith, D. H.
- Affiliations
- University of Pennsylvania (US)
- Venue
- Brain Pathology
- Publisher
- Wiley
- Published
- 2011-09-12
- Volume
- 22
- Issue
- 2
- Pages
- 142-149
- ISSN
- 1015-6305 (ISSN-L)
- 1750-3639
- PMC
- PMC3979351
- OpenAlex
- W2106837589
- Cited by
- 620
- References
- 45
- Citations by year
- 2026: 14 · 2025: 29 · 2024: 39 · 2023: 40 · 2022: 49 · 2021: 50 · 2020: 58 · 2019: 56 · 2018: 47 · 2017: 39 · 2016: 60 · 2015: 47 · 2014: 29 · 2013: 36 · 2012: 21
- FWCI
- 21.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Pathology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (R03AG038911)
- National Institute of Neurological Disorders and Stroke (NS-038104, R01NS038104, P01NS056202, NS 056202)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- traumatic brain injury, tau pathology, amyloid plaques, neurofibrillary tangles, chronic traumatic encephalopathy, diffuse plaques, postmortem brain, Alzheimer's disease, mild traumatic brain injury
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Brain Damage, Chronic, Brain Injuries, Female, Humans, Male, Middle Aged, Case-Control Studies, Amyloid beta-Peptides, Neurofibrillary Tangles, tau Proteins, Young Adult, Plaque, Amyloid
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