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Cited by 291Traumatic Brain Injury ResearchAlzheimer's disease research and treatmentsTraumatic Brain Injury and Neurovascular Disturbances

Beta-amyloid deposition in chronic traumatic encephalopathy

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Stein, Thor D., Montenigro, Philip H., Alvarez, Victor E., Xia, Weiming, Crary, John F., Tripodis, Yorghos, Daneshvar, Daniel H., Mez, Jesse +15 more·2015·Acta Neuropathologica
DOI 10.1007/s00401-015-1435-yPMC PMC4529056
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Abstract

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid β peptide (Aβ) levels, the extent of Aβ deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Aβ deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Aβ deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Aβ deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p < 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Aβ plaques and those without. Aβ deposition was significantly associated with the presence of the APOE ε4 allele (p = 0.035), older age at symptom onset (p < 0.001), and older age at death (p < 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (β = 2.43, p = 0.018), co-morbid Lewy body disease (OR = 5.01, p = 0.009), and dementia (OR = 4.45, p = 0.012). A subset of subjects met the diagnostic criteria for both CTE and AD, and in these subjects both Aβ plaques and total levels of Aβ1-40 were increased at the depths of the cortical sulcus compared to the gyral crests. Overall, these findings suggest that Aβ deposition is altered and accelerated in a cohort of CTE subjects compared to normal aging and that Aβ is associated with both pathological and clinical progression of CTE independent of age.

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  • Individuals with a history of repetitive head impacts and CTE may be at risk for multiple neurodegenerations including beta-amyloid deposition and Lewy body disease.

    “Moreover, individuals with a history of repetitive head impacts and CTE may be at risk for multiple neurodegenerations including bamyloid deposition (49) and Lewy body disease (50).”

    From Chronic Traumatic Encephalopathy Within an Amyotrophic Lateral Sclerosis Brain Bank Cohort (2018) · cites this paper as [49]

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Authors
Stein, T. D., Montenigro, P. H., Alvarez, V. E., Xia, W., Crary, J. F., Tripodis, Y., Daneshvar, D. H., Mez, J., Solomon, T., Meng, G., Kubilus, C. A., Cormier, K. A., Meng, S., Babcock, K., Kiernan, P., Murphy, L., Nowinski, C. J., Martin, B., Dixon, D., Stern, R. A., Cantu, R. C., Kowall, N. W., & McKee, A. C.
Affiliations
  • VA Boston Healthcare System (US)
  • Boston University (US)
  • Veterans Health Administration (US)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Stein, Thor D.
ORCID
Venue
Acta Neuropathologica
Publisher
Springer Science and Business Media LLC
Published
2015-05-06
Volume
130
Issue
1
Pages
21-34
ISSN
  • 0001-6322 (ISSN-L)
  • 1432-0533
DOI
10.1007/s00401-015-1435-y
PMC
PMC4529056
OpenAlex
W856139224
Cited by
291
References
10
Citations by year
2026: 14 · 2025: 18 · 2024: 14 · 2023: 24 · 2022: 16 · 2021: 29 · 2020: 42 · 2019: 28 · 2018: 30 · 2017: 34 · 2016: 30 · 2015: 10 · 2014: 2
FWCI
27.20
Type
journal article
Language
en
Open access
Licence
Locations
  • Acta Neuropathologica (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Veterans Affairs (Clinical Sciences Research and Development Merit Award)
  • Alzheimer's Association (NIRG-305779)
  • National Institute of Neurological Disorders and Stroke (U01NS086659-01)
  • National Institute on Aging (P30AG13846, supplement 0572063345-5)
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, amyloid-beta deposition, neuritic plaques, tauopathy, repetitive mild traumatic brain injury, APOE ε4, Lewy body disease, dementia, Alzheimer's disease, athletes, military veterans, age at symptom onset
MeSH terms
War-Related Injuries, Adult, Age Factors, Aged, Aged, 80 and over, Athletic Injuries, Brain, Humans, Middle Aged, Severity of Illness Index, Veterans, Cohort Studies, Comorbidity, Amyloid beta-Peptides, tau Proteins, Neurodegenerative Diseases, Brain Injury, Chronic, Apolipoprotein E4, Athletes, Plaque, Amyloid

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