Chronic traumatic encephalopathy pathology in multiple system atrophy
Open accessAbstract
Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder associated with repetitive traumatic brain injury. Multiple system atrophy (MSA) is a Parkinsonian disorder that can result in repetitive falls with associated head trauma. We hypothesized that patients with neurodegenerative disorders like MSA could develop CTE pathology. Therefore, we assessed CTE pathology in 139 MSA cases in our brain bank. Sections from convexity cerebral cortices were screened by immunohistochemistry with anti-phospho-tau antibody. For cases with suggestive CTE pathology, further sections of basal forebrain and hippocampus were immunostained. Consensus criteria were used to make the diagnosis of CTE and aging-related tau astrogliopathy (ARTAG) was differentiated from CTE pathology. Pertinent clinical information was derived from the available records and online searches. Of the 139 MSA cases, 8 (6%) had CTE pathology and 10 (8%) had ARTAG pathology. All 8 cases with CTE were male and 4 of them had a documented history of contact sports. The median age at death in MSA with CTE was younger than in MSA without CTE or MSA with ARTAG (60, 67, and 74 years, respectively; p = 0.002). Even without a known history of contact sports or head trauma, a small subset of cases with MSA had CTE pathology.
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P-tau in perivascular, subpial, and periventricular regions has recently been described in postmortem brains of patients with ALS, temporal lobe epilepsy, and multiple system atrophy but no known history of participation in contact sports or neurotrauma.
“P-tau in these regions has recently been described in the postmortem brains of patients who had ALS [31], temporal lobe epilepsy [32], and multiple system atrophy [33] but no known history of participation in contact sports or neurotrauma.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
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Experimental — accuracy not yet measuredThere are now several studies illustrating that CTE neuropathology, at the time of death, is limited to Stage I or less in many people.
“There are now several studies illustrating that CTE neuropathology, at the time of death, is limited to Stage I or less in many people [33, 37, 39]”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
The Neuropathologic Assessment of CTE reports that, among 139 people with multiple system atrophy, eight had CTE pathology: two were stage I, five stage II, and one stage III. This supports the existence of stage I pathology at death, but only two of the eight CTE cases were stage I; the study does not establish that CTE pathology is limited to stage I or less in many people generally. (LLM, conf=0.84)
Experimental — accuracy not yet measuredKoga et al. speculated that the CTE pathology could be related to falls associated with having multiple system atrophy, but there was no reported statistical association between falls and CTE pathology in that study.
“The authors speculated that the CTE pathology could be related to falls associated with having multiple system atrophy— but there was no reported statistical association between falls and CTE pathology in that study.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
In Koga et al., all CTE cases were men, but only four had a history of participation in sports.
“All were men, but only four had a history of participation in sports (three in football and one in basketball).”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
Koga and colleagues examined 139 autopsy-confirmed cases of multiple system atrophy for pathological evidence of CTE and identified CTE pathology in 8 cases (6%) using the consensus criteria.
“Koga and colleagues [33] examined 139 autopsy-confirmed cases of multiple system atrophy for pathological evidence of CTE. Using the consensus criteria, they identified CTE pathology in 8 cases (6%).”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
Koga et al. differentiated cases of ARTAG (10 cases) from CTE and noted that ARTAG pathology in past studies might have been mistaken for CTE pathology.
“The authors were careful to differentiate cases of ARTAG (10 cases) from CTE in this study, and noted that ARTAG pathology in past studies might have been mistaken for CTE pathology.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
In Koga et al., of the 8 CTE cases, two were Stage I, five Stage II, and one Stage III.
“They classified two cases as Stage I, five as Stage II, and one as Stage III.”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
It is now well-established that the pathology of CTE is present in people with other neurodegenerative diseases, such as AD, PD, and multiple system atrophy.
“Moreover, it is now well-established that the pathology of CTE is present in people with other neurodegenerative diseases, such as AD, PD, and multiple system atrophy”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [33]
The presence of comorbid ALS+CTE in an ALS cohort parallels similar findings of CTE in neurodegenerative cohorts, e.g. 6% in an MSA cohort, 6% in an American football CTE group, and 11.9%-32% in a group of various diseases.
“The presence of comorbid ALSþCTE in an ALS cohort parallel similar findings of CTE in neurodegenerative cohorts, e.g.6% in an multiple system atrophy (MSA) cohort as reported by Koga et al (46), 6% in an American football CTE group (47) and 11.9%-32% in a group of various diseases reported by Ling et al (48).”
From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [46]
The prevalence of CTE found in an MSA cohort is similar to the prevalence found in this study (5.8%).
“The prevalence of CTE found in an MSA cohort is similar to the prevalence found in this study (5.8%), and both populations are at a high risk of falls after the onset of neurological disease.”
From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [46]
When CTE pathology is found in studies that do not involve former collision or contact sport athletes, it is usually, but not always, reported that the subjects had a history of at least 1 brain injury, or the authors speculate that the subjects could have experienced undocumented brain injuries.
“When CTE pathology is found in studies that do not involve former collision or contact sport athletes, it is usually, but not always, reported that the subjects had a history of at least 1 brain injury (23), or the authors speculate that the subjects could have experienced injuries to their brains that were not documented, such as in falls (22).”
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 [22]
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References 23 · Cited by 58
Research works printed but not linked: 2
- Martland HS. Punch Drunk. Jama 1928;91:1103-7
- Millspaugh JA. Dementia pugilistica. US Naval Med Bull 1937;35: 297-303
- Authors
- Koga, S., Dickson, D. W., & Bieniek, K. F.
- Affiliations
- Mayo Clinic in Florida (US)
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-08-18
- Volume
- 75
- Issue
- 10
- Pages
- 963-970
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC5029441
- OpenAlex
- W2516101459
- Cited by
- 58
- References
- 23
- Citations by year
- 2025: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 11 · 2018: 9 · 2017: 14 · 2016: 3
- FWCI
- 11.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- CurePSP
- National Institutes of Health (AG016574, NS072187, AG003949)
- National Institute on Aging (P01AG003949, P50AG016574)
- National Institute of Neurological Disorders and Stroke (P50NS072187)
- Topics
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- chronic traumatic encephalopathy, multiple system atrophy, tau pathology, phosphorylated tau, repetitive head trauma, contact sports, neurodegeneration, basal forebrain, hippocampus
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