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Cited by 109Traumatic Brain Injury ResearchParkinson's Disease Mechanisms and TreatmentsAlzheimer's disease research and treatments

Lewy body pathology and chronic traumatic encephalopathy associated with contact sports

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Adams, Jason W, Alvarez, Victor E, Mez, Jesse, Huber, Bertrand R, Tripodis, Yorghos, Xia, Weiming, Meng, Gaoyuan, Kubilus, Caroline A +25 more·2018·Journal of Neuropathology & Experimental Neurology
DOI 10.1093/jnen/nly065PMC PMC6097837
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Abstract

Traumatic brain injury has been associated with increased risk of Parkinson disease and parkinsonism, and parkinsonism and Lewy body disease (LBD) can occur with chronic traumatic encephalopathy (CTE). To test whether contact sports and CTE are associated with LBD, we compared deceased contact sports athletes (n = 269) to cohorts from the community (n = 164) and the Boston University Alzheimer disease (AD) Center (n = 261). Participants with CTE and LBD were more likely to have β-amyloid deposition, dementia, and parkinsonism than CTE alone (p < 0.05). Traditional and hierarchical clustering showed a similar pattern of LBD distribution in CTE compared to LBD alone that was most frequently neocortical, limbic, or brainstem. In the community-based cohort, years of contact sports play were associated with neocortical LBD (OR = 1.30 per year, p = 0.012), and in a pooled analysis a threshold of >8 years of play best predicted neocortical LBD (ROC analysis, OR = 6.24, 95% CI = 1.5-25, p = 0.011), adjusting for age, sex, and APOE ɛ4 allele status. Clinically, dementia was significantly associated with neocortical LBD, CTE stage, and AD; parkinsonism was associated with LBD pathology but not CTE stage. Contact sports participation may increase risk of developing neocortical LBD, and increased LBD frequency may partially explain extrapyramidal motor symptoms sometimes observed in CTE.

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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 [50]

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Research works printed but not linked: 38

  1. Guerriero RM, Proctor MR, Mannix R, et al. Epidemiology, trends, as- sessment and management of sport-related concussion in United States high schools. Curr Opin Pediatr 2012;24:696-701
  2. Singh R, Meier TB, Kuplicki R, et al. Relationship of collegiate football experience and concussion with hippocampal volume and cognitive out- comes. JAMA 2014;311:1883-8
  3. Koerte IK, Lin AP, Muehlmann M, et al. Altered neurochemistry in for- mer professional soccer players without a history of concussion. J Neuro- trauma 2015;32:1287-93
  4. Poole VN, Abbas K, Shenk TE, et al. MR spectroscopic evidence of brain injury in the non-diagnosed collision sport athlete. Dev Neuropsychol 2014;39:459-73
  5. Nauman EA, Breedlove KM, Breedlove EL, et al. Post-season neuro- physiological deficits assessed by ImPACT and fMRI in athletes compet- ing in American football. Dev Neuropsychol 2015;40:85-91
  6. Stein TD, Alvarez VE, McKee AC. Concussion in chronic traumatic en- cephalopathy. Curr Pain Headache Rep 2015;19:522
  7. McKee AC, Stern RA, Nowinski CJ, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013;136:43-64
  8. Stein TD, Montenigro PH, Alvarez VE, et al. Beta-amyloid deposition in chronic traumatic encephalopathy. Acta Neuropathol 2015;130:21-34
  9. Cherry JD, Tripodis Y, Alvarez VE, et al. Microglial neuroinflammation contributes to tau accumulation in chronic traumatic encephalopathy. Acta Neuropathol Commun 2016;4:112
  10. Lehman EJ, Hein MJ, Baron SL, et al. Neurodegenerative causes of death among retired National Football League players. Neurology 2012;79: 1970-4
  11. Crane PK, Gibbons LE, Dams-O'Connor K, et al. Association of trau- matic brain injury with late-life neurodegenerative conditions and neuro- pathologic findings. JAMA Neurol 2016;73:1062
  12. Gardner RC, Burke JF, Nettiksimmons J, et al. Traumatic brain injury in later life increases risk for Parkinson disease. Ann Neurol 2015;77: 987-95
  13. Lee P-C, Bordelon Y, Bronstein J, et al. Traumatic brain injury, paraquat exposure, and their relationship to Parkinson disease. Neurology 2012; 79:2061-6
  14. Gardner RC, Byers AL, Barnes DE, et al. Mild TBI and risk of Parkinson disease. Neurology 2018;90:e1771-9
  15. Braak H, Del Tredici K, Ru ¨b U, et al. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging 2003;24:197-211
  16. Toledo JB, Gopal P, Raible K, et al. Pathological a-synuclein distribution in subjects with coincident Alzheimer's and Lewy body pathology. Acta Neuropathol 2016;131:393-409
  17. Uchikado H, Lin W-L, DeLucia MW, et al. Alzheimer disease with amygdala Lewy bodies: A distinct form of alpha-synucleinopathy. J Neu- ropathol Exp Neurol 2006;65:685-97
  18. Mez J, Solomon TM, Daneshvar DH, et al. Assessing clinicopathological correlation in chronic traumatic encephalopathy: Rationale and methods for the UNITE study. Alzheimers Res Ther 2015;7:62
  19. Beekly DL, Ramos EM, Lee WW, et al. The National Alzheimer's Coor- dinating Center (NACC) database: The uniform data set. Alzheimer Dis Assoc Disord 2007;21:249-58
  20. Vonsattel J-PG, Del Amaya MP, Keller CE. Twenty-first century brain banking. Processing brains for research: The Columbia University meth- ods. Acta Neuropathol 2008;115:509-32
  21. Hyman BT, Trojanowski JQ. Consensus recommendations for the post- mortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J Neuropathol Exp Neurol 1997;56:1095-7
  22. Mackenzie IRA, Neumann M, Bigio EH, et al. Nomenclature and nosol- ogy for neuropathologic subtypes of frontotemporal lobar degeneration: An update. Acta Neuropathol 2010;119:1-4
  23. Darby A, Adams JW, Babcock K, et al. Detection of CTE in autopsy cohorts using restricted cortical sampling. J Neuropathol Exp Neurol 2015;74:588-639
  24. Pearson ES. The analysis of variance in cases of non-normal variation. Biometrika 1931;23:114-33
  25. Ghajari M, Hellyer PJ, Sharp DJ. Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology. Brain 2017;140:333-43
  26. Rose G. Sick individuals and sick populations. Int J Epidemiol 2001;30: 427-32
  27. Burr e J, Sharma M, Tsetsenis T, et al. Alpha-synuclein promotes SNARE-complex assembly in vivo and in vitro. Science 2010;329: 1663-7
  28. Logan T, Bendor J, Toupin C, et al. a-Synuclein promotes dilation of the exocytotic fusion pore. Nat Neurosci 2017;20:681-9
  29. Vallortigara J, Whitfield D, Quelch W, et al. Decreased levels of VAMP2 and monomeric alpha-synuclein correlate with duration of de- mentia. J Alzheimers Dis 2016;50:101-10
  30. Mukaetova-Ladinska EB, Andras A, Milne J, et al. Synaptic proteins and choline acetyltransferase loss in visual cortex in dementia with Lewy bodies. J Neuropathol Exp Neurol 2013;72:53-60
  31. Campbell BCV, Li Q-X, Culvenor JG, et al. Accumulation of insoluble a- synuclein in dementia with lewy bodies. Neurobiol Dis 2000;7:192-200
  32. Mollenhauer B, Locascio JJ, Schulz-Schaeffer W, et al. a-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with par- kinsonism: A cohort study. Lancet Neurol 2011;10:230-40
  33. Toledo JB, Korff A, Shaw LM, et al. CSF a-synuclein improves diagnos- tic and prognostic performance of CSF tau and Ab in Alzheimer's dis- ease. Acta Neuropathol 2013;126:683-97
  34. Postupna N, Keene CD, Crane PK, et al. Cerebral cortical Ab42 and PHF-s in 325 consecutive brain autopsies stratified by diagnosis, loca- tion, and APOE. J Neuropathol Exp Neurol 2015;74:100-9
  35. Colom-Cadena M, Grau-Rivera O, Planellas L, et al. Regional overlap of pathologies in lewy body disorders. J Neuropathol Exp Neurol 2017;76: 216-24
  36. Gardner RC, Burke JF, Nettiksimmons J, et al. Dementia risk after trau- matic brain injury vs nonbrain trauma: The role of age and severity. JAMA Neurol 2014;71:14907
  37. Stern RA, Daneshvar DH, Baugh CM, et al. Clinical presentation of chronic traumatic encephalopathy. Neurology 2013;81:1122-9
  38. Alosco ML, Mez J, Tripodis Y, et al. Age of first exposure to tackle foot- ball and chronic traumatic encephalopathy. Ann Neurol 2018;83:886-901.

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Authors
Adams, J. W., Alvarez, V. E., Mez, J., Huber, B. R., Tripodis, Y., Xia, W., Meng, G., Kubilus, C. A., Cormier, K., Kiernan, P. T., Daneshvar, D. H., Chua, A. S., Svirsky, S., Nicks, R., Abdolmohammadi, B., Evers, L., Solomon, T. M., Cherry, J. D., Aytan, N., Mahar, I., Devine, S., Auerbach, S., Alosco, M. L., Nowinski, C. J., Kowall, N. W., Goldstein, L. E., Dwyer, B., Katz, D. I., Cantu, R. C., Stern, R. A., Au, R., McKee, A. C., & Stein, T. D.
Affiliations
  • Boston University (US)
  • VA Boston Healthcare System (US)
  • Department of Neurology
Corresponding author
Stein, Thor D
ORCID
Venue
Journal of Neuropathology & Experimental Neurology
Publisher
Oxford University Press (OUP)
Published
2018-07-25
Volume
77
Issue
9
Pages
757-768
ISSN
  • 0022-3069 (ISSN-L)
  • 1554-6578
DOI
10.1093/jnen/nly065
PMC
PMC6097837
OpenAlex
W2883611426
Cited by
109
References
9
Citations by year
2026: 9 · 2025: 13 · 2024: 10 · 2023: 21 · 2022: 13 · 2021: 12 · 2020: 11 · 2019: 16 · 2018: 4
FWCI
8.39
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Neuropathology & Experimental Neurology (publishedVersion, public-domain)
  • Europe PMC (PubMed Central) (publishedVersion, public-domain)
  • PubMed Central (publishedVersion, public-domain)
  • PubMed (publishedVersion)
Funders
  • Department of Veterans Affairs
  • Veterans Health Administration
  • Clinical Sciences Research and Development (I01-CX001038)
  • Veterans Affairs Biorepository (BX002466)
  • Alzheimer’s Association (NIRG-305779, NIRG-362697)
  • National Institute of Aging (RF1AG054156, R56AG057768, K23AG046377, R01AG016495, R01AG008122, R01AG033040)
  • National Institute of Neurological Disorders and Stroke (U01NS086659, F32NS096803, R01NS017950)
  • National Institute of Aging Boston University AD Center (P30AG13846)
  • Department of Defense Peer Reviewed Alzheimer’s Research Program (PRARP #13267017)
  • National Heart, Lung, and Blood Institute (N01-HC-25195, HHSN268201500001I)
  • Fonds de Recherche du Québec—Santé
  • Andlinger Foundation and WWE
Topics
  • Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
Lewy body disease, chronic traumatic encephalopathy, contact sports, traumatic brain injury, Parkinson's disease, parkinsonism, amyloid-beta deposition, dementia, APOE ε4
MeSH terms
Chronic Traumatic Encephalopathy, Adolescent, Adult, Aged, Aged, 80 and over, Apolipoproteins E, Brain, Female, Humans, Male, Middle Aged, Sports, Cohort Studies, Trauma Severity Indices, Amyloid beta-Peptides, Lewy Bodies, tau Proteins, Polymorphism, Single Nucleotide, Lewy Body Disease, alpha-Synuclein, Young Adult

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