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A critical review of chronic traumatic encephalopathy
Abstract
Chronic traumatic encephalopathy (CTE) has been described in the literature as a neurodegenerative disease with: (i) localized neuronal and glial accumulations of phosphorylated tau (p-tau) involving perivascular areas of the cerebral cortex, sulcal depths, and with a preference for neurons within superficial cortical laminae; (ii) multifocal axonal varicosities and axonal loss involving deep cortex and subcortical white matter; (iii) relative absence of beta-amyloid deposits; (iv) TDP-43 immunoreactive inclusions and neurites; and (v) broad and diverse clinical features. Some of the pathological findings reported in the literature may be encountered with age and other neurodegenerative diseases. However, the focality of the p-tau cortical findings in particular, and the regional distribution, are believed to be unique to CTE. The described clinical features in recent cases are very similar to how depression manifests in middle-aged men and with frontotemporal dementia as the disease progresses. It has not been established that the described tau pathology, especially in small amounts, can cause complex changes in behavior such as depression, substance abuse, suicidality, personality changes, or cognitive impairment. Future studies will help determine the extent to which the neuropathology is causally related to the diverse clinical features.
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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 [29]
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Metadata
- Authors
- Iverson, G. L., Gardner, A. J., McCrory, P., Zafonte, R., & Castellani, R. J.
- Affiliations
- Harvard University (US)
- Hunter New England Local Health District (AU)
- Florey Institute of Neuroscience and Mental Health (AU)
- Brigham and Women's Hospital (US)
- University of Maryland, Baltimore (US)
- Corresponding author
- Iverson, Grant L.
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 56
- Pages
- 276-293
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W929294836
- Cited by
- 103
- References
- 228
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 3 · 2022: 4 · 2021: 8 · 2020: 10 · 2019: 12 · 2018: 12 · 2017: 23 · 2016: 20 · 2015: 2
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion)
- PubMed (publishedVersion)
- NOVA (University of Newcastle Australia) (submittedVersion)
- 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, tau phosphorylation, axonal varicosities, axonal loss, TDP-43 inclusions, amyloid-beta, neurodegeneration, depression, frontotemporal dementia, behavioral symptoms, cognitive impairment, neuropathology
- MeSH terms
- Cognition Disorders, Dementia, DNA-Binding Proteins, Humans, tau Proteins, Disease Progression, Brain Injury, Chronic
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