Current Genetic Medicine Reports

, Volume 3, Issue 4, pp 191–195 | Cite as

Genetics and Pathology of Chronic Traumatic Encephalopathy

  • Laura L. Krafjack
  • Ramesh RaghupathiEmail author
Neurogenetics and Psychiatric Genetics (M Hiltunen & DR Marenda, Section Editors)
Part of the following topical collections:
  1. Neurogenetics and Psychiatric Genetics


Chronic traumatic encephalopathy (CTE), characterized by the presence of neurofibrillary and astrocytic tangles composed of hyperphosphorylated tau, is believed to be one of the pathological consequences of repetitive traumatic brain injury (TBI). CTE has been diagnosed post-mortem in numerous individuals, including professional boxers and American football players, with a history of repetitive TBI [1, 2••, 3, 4, 5, 6, 7]. Concomitant with the identification of these neurofibrillary and astrocytic tangles are retrospective reports from family members and friends of these individuals of memory problems and personality changes, suggesting that the observed pathological changes may underlie the reported behavioral changes. Multiple animal models have been developed to further explore how repetitive TBI results in these pathological findings and whether these alterations underlie behavioral changes.

Defining CTE and Limitations of Diagnosis

As more cases of CTE are identified,...


Traumatic Brain Injury Amyotrophic Lateral Sclerosis Chronic Traumatic Encephalopathy Traumatic Brain Injury Model American Football Player 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The support was received, in part, from grants from the National Institutes of Neurologic Disorders and Stroke (NS 065017) and National Institutes of Child Health and Development (NS 069163).


Papers of particular interest published in the last three years have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Geddes JF, Vowles GH, Nicoll JA, Revesz T. Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol. 1999;98(2):171–8.CrossRefPubMedGoogle Scholar
  2. 2.
    •• Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery. 2005;57(1):128–34 discussion-34. This was the first report of CTE in a brain of an individual who was subjected to multiple TBIs during his playing career. Google Scholar
  3. 3.
    Omalu BI, DeKosky ST, Hamilton RL, Minster RL, Kamboh MI, Shakir AM, et al. Chronic traumatic encephalopathy in a national football league player: part II. Neurosurgery. 2006;59(5):1086–92 discussion 92–3.PubMedGoogle Scholar
  4. 4.
    Omalu BI, Fitzsimmons RP, Hammers J, Bailes J. Chronic traumatic encephalopathy in a professional American wrestler. J Forensic Nurs. 2010;6(3):130–6.CrossRefPubMedGoogle Scholar
  5. 5.
    McKee AC, Gavett BE, Stern RA, Nowinski CJ, Cantu RC, Kowall NW, et al. TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy. J Neuropathol Exp Neurol. 2010;69(9):918–29.PubMedCentralCrossRefPubMedGoogle Scholar
  6. 6.
    Omalu B, Bailes J, Hamilton RL, Kamboh MI, Hammers J, Case M, et al. Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery. 2011;69(1):173–83 discussion 83.CrossRefPubMedGoogle Scholar
  7. 7.
    Hazrati LN, Tartaglia MC, Diamandis P, Davis KD, Green RE, Wennberg R, et al. Absence of chronic traumatic encephalopathy in retired football players with multiple concussions and neurological symptomatology. Front Hum Neurosci. 2013;7:222.PubMedCentralCrossRefPubMedGoogle Scholar
  8. 8.
    McKee AC, Stern RA, Nowinski CJ, Stein TD, Alvarez VE, Daneshvar DH, et al. The spectrum of disease in chronic traumatic encephalopathy. Brain. 2013;136(Pt 1):43–64.PubMedCentralCrossRefPubMedGoogle Scholar
  9. 9.
    Baugh CM, Stamm JM, Riley DO, Gavett BE, Shenton ME, Lin A, et al. Chronic Traumatic encephalopathy: neurodegeneration following repetitive concussive and subconcussive brain trauma. Brain Imaging Behav. 2012;6:244–54. Google Scholar
  10. 10.
    Guskiewicz KM, Marshall SW, Bailes J, McCrea M, Cantu RC, Randolph C, et al. Association between recurrent concussion and late-life cognitive impairment in retired professional football players. Neurosurgery. 2005;57(4):719–26 discussion-26.CrossRefPubMedGoogle Scholar
  11. 11.
    Casson IR, Viano DC, Haacke EM, Kou Z, LeStrange DG. Is there chronic brain damage in retired NFL players? Neuroradiology, neuropsychology, and neurology examinations of 45 retired players. Sports Health. 2014;6(5):384–95.PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    •• Montenigro PH, Bernick C, Cantu RC. Clinical features of repetitive traumatic brain injury and chronic traumatic encephalopathy. Brain Pathol. 2015;25(3):304–17. This review gives the most current and extensive characterization of the cognitive, emotional, and physical symptoms associated with CTE. Google Scholar
  13. 13.
    Kanekiyo T, Xu H, Bu G. ApoE and Abeta in Alzheimer’s disease: accidental encounters or partners? Neuron. 2014;81(4):740–54.PubMedCentralCrossRefPubMedGoogle Scholar
  14. 14.
    Teasdale GM, Nicoll JA, Murray G, Fiddes M. Association of apolipoprotein E polymorphism with outcome after head injury. Lancet. 1997;350(9084):1069–71.CrossRefPubMedGoogle Scholar
  15. 15.
    Omalu BI, Hamilton RL, Kamboh MI, DeKosky ST, Bailes J. Chronic traumatic encephalopathy (CTE) in a National Football League Player: case report and emerging medicolegal practice questions. J Forensic Nurs. 2010;6(1):40–6.CrossRefPubMedGoogle Scholar
  16. 16.
    Goldstein LE, Fisher AM, Tagge CA, Zhang XL, Velisek L, Sullivan JA, et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med. 2012;4(134):134ra60.PubMedCentralCrossRefPubMedGoogle Scholar
  17. 17.
    •• McKee AC, Stein TD, Kiernan PT, Alvarez VE. The neuropathology of chronic traumatic encephalopathy. Brain Pathol. 2015;25(3):350–64. This review summarizes the most current pathological characterizations of CTE. Google Scholar
  18. 18.
    Hof PR, Knabe R, Bovier P, Bouras C. Neuropathological observations in a case of autism presenting with self-injury behavior. Acta Neuropathol. 1991;82(4):321–6.CrossRefPubMedGoogle Scholar
  19. 19.
    Roberts GW, Whitwell HL, Acland PR, Bruton CJ. Dementia in a punch-drunk wife. Lancet. 1990;335(8694):918–9.CrossRefPubMedGoogle Scholar
  20. 20.
    Yoshiyama Y, Uryu K, Higuchi M, Longhi L, Hoover R, Fujimoto S, et al. Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model. J Neurotrauma. 2005;22(10):1134–41.CrossRefPubMedGoogle Scholar
  21. 21.
    Miyauchi T, Wei EP, Povlishock JT. Therapeutic targeting of the axonal and microvascular change associated with repetitive mild traumatic brain injury. J Neurotrauma. 2013;30(19):1664–71.PubMedCentralCrossRefPubMedGoogle Scholar
  22. 22.
    Miyauchi T, Wei EP, Povlishock JT. Evidence for the therapeutic efficacy of either mild hypothermia or oxygen radical scavengers after repetitive mild traumatic brain injury. J Neurotrauma. 2014;31(8):773–81.PubMedCentralCrossRefPubMedGoogle Scholar
  23. 23.
    Petraglia AL, Plog BA, Dayawansa S, Chen M, Dashnaw ML, Czerniecka K, et al. The spectrum of neurobehavioral sequelae after repetitive mild traumatic brain injury: a novel mouse model of chronic traumatic encephalopathy. J Neurotrauma. 2014;31(13):1211–24.PubMedCentralCrossRefPubMedGoogle Scholar
  24. 24.
    Donovan V, Kim C, Anugerah AK, Coats JS, Oyoyo U, Pardo AC, et al. Repeated mild traumatic brain injury results in long-term white-matter disruption. J Cereb Blood Flow Metab. 2014;34(4):715–23.PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Longhi L, Saatman KE, Fujimoto S, Raghupathi R, Meaney DF, Davis J, et al. Temporal window of vulnerability to repetitive experimental concussive brain injury. Neurosurgery. 2005;56(2):364–74.CrossRefPubMedGoogle Scholar
  26. 26.
    Bolton AN, Saatman KE. Regional neurodegeneration and gliosis are amplified by mild traumatic brain injury repeated at 24-hour intervals. J Neuropathol Exp Neurol. 2014;73(10):933–47.PubMedCentralCrossRefPubMedGoogle Scholar
  27. 27.
    Mannix R, Meehan WP, Mandeville J, Grant PE, Gray T, Berglass J, et al. Clinical correlates in an experimental model of repetitive mild brain injury. Ann Neurol. 2013;74(1):65–75.CrossRefPubMedGoogle Scholar
  28. 28.
    Ojo JO, Mouzon B, Greenberg MB, Bachmeier C, Mullan M, Crawford F. Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice. J Neuropathol Exp Neurol. 2013;72(2):137–51.CrossRefPubMedGoogle Scholar
  29. 29.
    Shitaka Y, Tran HT, Bennett RE, Sanchez L, Levy MA, Dikranian K, et al. Repetitive closed-skull traumatic brain injury in mice causes persistent multifocal axonal injury and microglial reactivity. J Neuropathol Exp Neurol. 2011;70(7):551–67.PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Kane MJ, Angoa-Perez M, Briggs DI, Viano DC, Kreipke CW, Kuhn DM. A mouse model of human repetitive mild traumatic brain injury. J Neurosci Methods. 2012;203(1):41–9.PubMedCentralCrossRefPubMedGoogle Scholar
  31. 31.
    Mouzon B, Chaytow H, Crynen G, Bachmeier C, Stewart J, Mullan M, et al. Repetitive mild traumatic brain injury in a mouse model produces learning and memory deficits accompanied by histological changes. J Neurotrauma. 2012;29(18):2761–73.CrossRefPubMedGoogle Scholar
  32. 32.
    Mannix R, Berglass J, Berkner J, Moleus P, Qiu J, Andrews N, et al. Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury. J Neurosurg. 2014;121:1342–50.Google Scholar
  33. 33.
    Aungst SL, Kabadi SV, Thompson SM, Stoica BA, Faden AI. Repeated mild traumatic brain injury causes chronic neuroinflammation, changes in hippocampal synaptic plasticity, and associated cognitive deficits. J Cereb Blood Flow Metab. 2014;34(7):1223–32.PubMedCentralCrossRefPubMedGoogle Scholar
  34. 34.
    Bennett RE, Brody DL. Acute reduction of microglia does not alter axonal injury in a mouse model of repetitive concussive traumatic brain injury. J Neurotrauma. 2014;31(19):1647–63.PubMedCentralCrossRefPubMedGoogle Scholar
  35. 35.
    Luo J, Nguyen A, Villeda S, Zhang H, Ding Z, Lindsey D, et al. Long-term cognitive impairments and pathological alterations in a mouse model of repetitive mild traumatic brain injury. Front Neurol. 2014;5:12.PubMedCentralCrossRefPubMedGoogle Scholar
  36. 36.
    • Randolph C. Is chronic traumatic encephalopathy a real disease? Curr Sports Med Rep. 2014;13(1):33–7. This opinion piece questions the validity of the published data as being supportive of a “new” disease, i.e. CTE as opposed to a variant of neurodegenerative diseases such as AD, FTD, PD, etc. Google Scholar

Copyright information

© Springer Science + Business Media New York 2015

Authors and Affiliations

  1. 1.Program in NeuroscienceDrexel University College of MedicinePhiladelphiaUSA
  2. 2.Department of Neurobiology and AnatomyDrexel University College of MedicinePhiladelphiaUSA
  3. 3.Coatesville Veteran’s Administration Medical CenterCoatesvilleUSA

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