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Cited by 323Traumatic Brain Injury ResearchAlzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular Disturbances

Neuronal cytoskeletal changes are an early consequence of repetitive head injury

Geddes, J. F., Vowles, G. H., Nicoll, J. A. R., Révész, T.·1999·Acta Neuropathologica
DOI 10.1007/s004010051066
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Abstract

While neuropathological studies have established the pathology of dementia pugilistica to be similar to that of Alzheimer's disease, there is little information about the early histological changes caused by the repetitive trauma that eventually produces dementia pugilistica. We have examined the brains of four young men and a frontal lobectomy specimen from a fifth, age range 23-28 years, all of whom suffered mild chronic head injury. There were two boxers, a footballer, a mentally subnormal man with a long history of head banging, and an epileptic patient who repeatedly hit his head during seizures. The four autopsy cases were widely sampled; the lobectomy specimen was serially sliced after fixation. Routine stains were performed; inmmunostaining included beta-amyloid precursor protein, amyloid beta-protein (Abeta), tau and apolipoprotein E (apoE). Pathological findings in all five cases were of neocortical neurofibrillary tangles (NFTs) and neuropil threads, with groups of tangles consistently situated around blood vessels in the worst affected regions. No Abeta immunoreactivity was detected. The amount of neuronal apoE expression varied widely between the cases with no clear relation to the NFTs. The apoE genotype was determined in only two cases (both epsilon3/epsilon3). It appears that repetitive head injury in young adults is initially associated with neocortical NFT formation in the absence of Abeta deposition. The distribution of the tau pathology suggests that the pathogenesis of cytoskeletal abnormalities may involve damage to blood vessels or perivascular elements.

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  • The conspicuous perivascular nature of neurofibrillary pathology and its tendency to be irregularly concentrated at the sulcal depths of the cortex in CTE were first noted by Geddes.

    “The conspicuous perivascular nature of the neurofibrillary pathology and its tendency to be irregularly concentrated at the sulcal depths of the cortex in CTE were first noted by Geddes in her description of the neuropathological alterations of five young men, 23– 28 years old, including two boxers, one soccer player, one developmentally challenged individual with a long history of head banging, a”

    From The neuropathology of sport (2014) · cites this paper as [65]

  • The clinical symptoms associated with CTE were examined in case summaries throughout the twentieth century; however, the disease presentation described in these reports was inconsistent.

    “The clinical symptoms associated with this disease were examined in case summaries throughout the twentieth century; however, the disease presentation described in these reports was inconsistent [38, 65, 92, 100, 126].”

    From The neuropathology of sport (2014) · cites this paper as [65]

  • Geddes described argyrophilic, PHF-tau positive neocortical NFTs and neurites arranged in groups around small intracortical blood vessels in the absence of Ab, a feature that distinguishes early CTE from other tauopathies.

    “Geddes described argyrophilic, PHF-tau positive neocortical NFTs and neurites, strikingly arranged in groups around small intracortical blood vessels, in the absence of Ab [65], a feature that has recently been found to distinguish even early stages of CTE from other tauopathies.”

    From The neuropathology of sport (2014) · cites this paper as [65]

  • Despite evidence for Ab deposition in moderate to severe TBI, Ab plaques have not been found in early or mild stages of CTE in young individuals, but occur in older subjects with CTE in association with increased age at death.

    “However, despite evidence for Ab deposition in moderate to severe TBI [94], Ab plaques have not been found in early or mild stages of CTE in young individuals [65, 66, 72, 91, 126] but occur in older subjects with CTE in association with increased age at death [128].”

    From The neuropathology of sport (2014) · cites this paper as [65]

  • CTE has been diagnosed neuropathologically in American football players, professional and amateur boxers, ice hockey players, professional wrestlers, soccer players, rugby players, and a professional baseball player.

    “Although CTE was first identified in association with boxing, CTE has been diagnosed neuropathologically in American football players, professional and amateur boxers, ice hockey players, professional wrestlers, soccer players, rugby players, and a professional baseball player (Figs. 3, 4, 5, 6) [38, 65, 66, 88, 91, 127, 128, 146–148].”

    From The neuropathology of sport (2014) · cites this paper as [65]

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Authors
Geddes, J. F., Vowles, G. H., Nicoll, J. A. R., & Révész, T.
Affiliations
  • St Bartholomew's Hospital (GB)
  • University of Glasgow (GB)
  • UCL Queen Square Institute of Neurology (GB)
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
1999-08-06
Volume
98
Issue
2
Pages
171-178
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s004010051066
OpenAlex
W1977627126
Cited by
323
References
60
Citations by year
2026: 3 · 2025: 11 · 2024: 8 · 2023: 14 · 2022: 17 · 2021: 14 · 2020: 15 · 2019: 22 · 2018: 20 · 2017: 19 · 2016: 27 · 2015: 20 · 2014: 15 · 2013: 18 · 2012: 12
FWCI
6.03
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Imperial College London
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
repetitive head injury, chronic traumatic encephalopathy, neurofibrillary tangles, neuropil threads, tau protein, amyloid-beta, apolipoprotein E, neuronal cytoskeleton, blood vessel damage, boxing, young adults
MeSH terms
Adult, Apolipoproteins E, Brain, Brain Diseases, Calcinosis, Cytoskeleton, Epilepsy, Hamartoma, Craniocerebral Trauma, Humans, Male, Neurons, Time Factors, Neurofibrillary Tangles, tau Proteins, Fatal Outcome, Apolipoprotein E3

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