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Chronic Effects of Mild Neurotrauma: Putting the Cart Before the Horse?
Open accessAbstract
Accumulation of phosphorylated tau (p-tau) is accepted by many as a long-term consequence of repetitive mild neurotrauma based largely on brain findings in boxers (dementia pugilistica) and, more recently, former professional athletes, military service members, and others exposed to repetitive head trauma. The pathogenic construct is also largely accepted and suggests that repetitive head trauma (typically concussions or subconcussive forces) acts on brain parenchyma to produce a deleterious neuroinflammatory cascade, encompassing p-tau templating, transsynaptic neurotoxicity, progressive neurodegenerative disease, and associated clinical features. Some caution before accepting these concepts and assumptions is warranted, however. The association between the history of concussion and findings of p-tau at autopsy is unclear. Concussions and subconcussive head trauma exposure are poorly defined in available cases, and the clinical features reported in chronic traumatic encephalopathy are not at present distinguishable from other disorders. Because control groups are limited, the idea that p-tau drives the disease process via protein templating or some other mechanism is preliminary. Much additional research in chronic traumatic encephalopathy is needed to determine if it has unique neuropathology and clinical features, the extent to which the neuropathologic alterations cause the clinical features, and whether it can be identified accurately in a living person.
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“Most of the above-mentioned gross and microscopic features have not, as yet, been independently verified as specific to CTE [27–30], and virtually all are associated with aging, other neurological diseases, or both.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [27]
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Metadata
- Authors
- Castellani, R. J., Perry, G., & Iverson, G. L.
- Affiliations
- University of Maryland, Baltimore (US)
- The University of Texas at San Antonio (US)
- Harvard University (US)
- Corresponding author
- Castellani, Rudy J.
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-06
- Volume
- 74
- Issue
- 6
- Pages
- 493-499
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC4433573
- OpenAlex
- W2319583242
- Cited by
- 40
- References
- 67
- Citations by year
- 2026: 3 · 2024: 2 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 4 · 2019: 9 · 2018: 2 · 2017: 6 · 2016: 7 · 2015: 3
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Minority Health and Health Disparities (G12MD007591)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- chronic traumatic encephalopathy, phosphorylated tau, concussion, protein templating, neuroinflammation, neuropathology, former athletes, military personnel
- MeSH terms
- Brain, Humans, Databases, Bibliographic, tau Proteins, Brain Injury, Chronic
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