Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank
Open accessAbstract
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.
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Of the 7 with Stage I pathology, two died with ALS; of the 5 who did not have ALS, 4 were over the age of 70 at the time of their death, suggesting that the CTE pathology had not or had minimally progressed over their adult lives.
“Of the 7 with Stage I pathology, two died with ALS. Of the 5 who did not have ALS, 4 were over the age of 70 at the time of their death, suggesting that the CTE pathology had not or had minimally progressed over their adult lives.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [38]
The Results (page unavailable) report seven Stage I CTE cases and three ALS cases among all 21 people with CTE pathology. They do not identify two ALS cases within Stage I or state that four of the remaining five died after age 70. The Discussion (page unavailable) describes Stages I and II as mild to moderate pathology but does not assess how little pathology progressed over these individuals’ adult lives. (LLM, conf=0.84)
Experimental — accuracy not yet measuredIn another study, all 21 cases of CTE pathology had a separate neurodegenerative disease.
“In another study [38], 21 of 66 former athletes (31.8%) had tau pathology suggestive of CTE. All cases had a separate neurodegenerative disease.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [38]
The Results report CTE-consistent pathology in 21 of 66 men with contact-sport exposure, supporting the first part of the cited sentence. But they identify a previously defined neurodegenerative condition in 20 of those 21 patients, not all 21. The copy provides no page number for these passages. (LLM, conf=0.93)
Experimental — accuracy not yet measuredIn that study, nearly all (95%; 20/21) of those with CTE pathology had primary neuropathological diagnoses of a neurodegenerative disease such as AD, frontotemporal dementia, Lewy body disease, or ALS.
“Nearly all (95%; 20/21) of those with CTE pathology had primary neuropathological diagnoses of a neurodegenerative disease such as AD, frontotemporal dementia, Lewy body disease, or ALS.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [38]
In that study, 2 of 9 (22.2%) former boxers and 16 of 43 (37.2%) former football players had CTE pathology.
“Of the former boxers, 2 of 9 (22.2%) had CTE pathology and 16 of 43 former football players (37.2%) had CTE pathology.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [38]
In another large-scale neuropathology study, 21 of 66 former athletes (31.8%) had tau pathology suggestive of CTE.
“In another large-scale neuropathology study [38], 21 of 66 former athletes (31.8%) had tau pathology suggestive of CTE.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [38]
If the CTE pathology represented a separate progressive neurodegenerative disease, it would be expected that former athletes with CTE, compared to those without CTE, would have earlier onset clinical features of disease and earlier death; however, there were no differences between groups in disease onset, disease duration, or age at death.
“Moreover, if the CTE pathology represented a separate progressive neurodegenerative disease, it would be expected that former athletes with CTE, compared to those without CTE, would have earlier onset clinical features of disease and earlier death. However, there were no differences between groups in disease onset, disease duration, or age at death [38].”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [38]
Incidence estimates for ALS range from about 2 to 3 per 100,000 people per year; ALS is more common in males and military veterans.
“Incidence estimates for ALS range from about 2 to 3 per 100 000 people per year; ALS is more common in males and military veterans (11,12).”
From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [11]
Split into 2 atoms — 0 confirmed, 0 partially supported, 0 disputed, 0 misattributed, 2 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredIn a large-scale neuropathology study, a subgroup of 33 patients with at least 1 TBI from motor vehicle accidents, assaults, domestic violence, or falls had none with neuropathology characteristic of CTE.
“In a large-scale neuropathology study, a subgroup of 33 patients was identified as having at least 1 TBI from motor vehicle accidents, assaults, domestic violence, or falls, and none of these individuals had the neuropathology characteristic of CTE (34).”
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 [34]
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- Authors
- Bieniek, K. F., Ross, O. A., Cormier, K. A., Walton, R. L., Soto-Ortolaza, A., Johnston, A. E., DeSaro, P., Boylan, K. B., Graff-Radford, N. R., Wszolek, Z. K., Rademakers, R., Boeve, B. F., McKee, A. C., & Dickson, D. W.
- Affiliations
- Mayo Clinic (US)
- Mayo Clinic in Florida (US)
- VA Boston Healthcare System (US)
- Boston University (US)
- Corresponding author
- Dickson, Dennis W.
- ORCID
- Venue
- Acta Neuropathologica
- Published
- 2015-10-30
- Volume
- 130
- Issue
- 6
- Pages
- 877-889
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC4655127
- OpenAlex
- W1944945174
- Cited by
- 323
- References
- 39
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 24 · 2023: 33 · 2022: 23 · 2021: 32 · 2020: 31 · 2019: 33 · 2018: 29 · 2017: 35 · 2016: 30 · 2015: 2
- FWCI
- 25.09
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (P50 NS072187, R01 NS076471, R01 NS078086, UO1 NS086659-01, P30 AG13846)
- 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
- chronic traumatic encephalopathy, repetitive traumatic brain injury, contact sports, hyperphosphorylated tau, neurodegenerative diseases, apolipoprotein E, MAPT, TMEM106B, genetic risk variants, brain banks
- MeSH terms
- Aged, Apolipoproteins E, Athletic Injuries, Brain, Female, Humans, Immunohistochemistry, Male, Membrane Proteins, Nerve Tissue Proteins, Retrospective Studies, Tissue Banks, tau Proteins, Neurodegenerative Diseases, Brain Injury, Chronic
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