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13 - Polypathology and Dementia After Brain Trauma: Does Brain Injury Trigger Distinct Neurodegenerative Diseases, or Should They Be Classified Together as Traumatic Encephalopathy?

from Part II - Outcomes after Concussion

Published online by Cambridge University Press:  22 February 2019

By
Patricia M.Washington ,
Sonia Villapol  and
Mark P. Burns
Edited by
Jeff Victoroff  and
Erin D. Bigler
Jeff Victoroff
Affiliation:
University of Southern California, Torrance
Erin D. Bigler
Affiliation:
Brigham Young University, Utah
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Summary

This volume has already established, in so far as our very limited current knowledge allows, that: (a) brain changes may persist after single concussive brain injuries; (b) brain changes may develop after an apparently asymptomatic period following multiple CBIs; and that (c) survivors of atypical CBIs that have prolonged loss of consciousness appear at higher risk of developing brain changes that have been called "neurodegenerative diseases," with popular labels such as "Parkinson's disease" and "Alzheimer's disease." Insufficient research has occurred to determine whether single typical CBIs might also increase the risk for delayed-onset encephalopathy. Today's implausible classification of time-passing-related brain changes makes it more difficult to study the relationship between these observations. The present chapter attempts to bring some coherence to that discussion by reviewing epidemiological studies of encephalopathy after CBI, by considering the long-term influence of post-traumatic neurodegenerative pathologies, and by critically examining the hypothesis that trauma is a risk factor for otherwise conventional dementing illnesses.
Type
Chapter
Information
Concussion and Traumatic Encephalopathy
Causes, Diagnosis and Management
 , pp. 573 - 581
Publisher: Cambridge University Press
Print publication year: 2019

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References

Martland, H.S., 1928. Punch drunk. J. Am. Med. Assoc. 91, 1103–1107.CrossRefGoogle Scholar
Langlois, J.A., Rutland-Brown, W., Wald, M.M., 2006. The epidemiology and impact of traumatic brain injury: a brief overview. J. Head Trauma Rehabil. 21, 375–378.Google Scholar
Osnato, M., Giliberti, V., 1927. Postconcussion neurosis – traumatic encephalitis: a conception of postconcussion phenomena. Arch. Neurol. Psychiatry 18, 181–214.CrossRefGoogle Scholar
Millspaugh, H.S., 1937. Dementia pugilistica. U. S. Med. Bull. 35, 297–303.Google Scholar
McCown, I.A., 1959. Boxing injuries. Am. J. Surg. 98, 509–516.Google Scholar
Smith, D.H., Johnson, V.E., Stewart, W., 2013. Chronic neuropathologies of single and repetitive TBI: substrates of dementia? Nat. Rev. Neurol. 9, 211–221.CrossRefGoogle ScholarPubMed
McKee, A.C., Stein, T.D., Nowinski, C.J., Stern, R.A., Daneshvar, D.H., Alvarez, V.E., et al., 2013. The spectrum of disease in chronic traumatic encephalopathy. Brain 136, 43–64.Google Scholar
Shalat, S.L., Seltzer, B., Pidcock, C., Baker Jr., E.L., 1987. Risk factors for Alzheimer’s disease: a case–control study. Neurology 37, 1630–1633.Google Scholar
Katzman, R., Aronson, M., Fuld, P., Kawas, C., Brown, T., Morgenstern, H., Frishman, W., Gidez, L., Eder, H., Ooi, W.L., 1989. Development of dementing illnesses in an 80-year-old volunteer cohort. Ann. Neurol. 25, 317–324.Google Scholar
Broe, G.A., Henderson, A.S., Creasey, H., McCusker, E., Korten, A.E., Jorm, A.F., Longley, W., Anthony, J.C., 1990. A case–control study of Alzheimer’s disease in Australia. Neurology 40, 1698–1707.Google Scholar
Fratiglioni, L., Ahlbom, A., Viitanen, M., Winblad, B., 1993. Risk factors for late-onset Alzheimer’s disease: a population-based, case–control study. Ann. Neurol. 33, 258–266.Google Scholar
Tsolaki, M., Fountoulakis, K., Chantzi, E., Kazis, A., 1997. Risk factors for clinically diagnosed Alzheimer’s disease: a case–control study of a Greek population. Int. Psychogeriatr. 9, 327–341.Google Scholar
O’Meara, E.S., Kukull, W.A., Sheppard, L., Bowen, J.D., McCormick, W.C., Teri, L., Pfanschmidt, M., Thompson, J.D., Schellenberg, G.D., Larson, E.B., 1997. Head injury and risk of Alzheimer’s disease by apolipoprotein E genotype. Am. J. Epidemiol. 146, 373–384.CrossRefGoogle ScholarPubMed
Rasmusson, D.X., Brandt, J., Martin, D.B., Folstein, M.F., 1995. Head injury as a risk factor in Alzheimer’s disease. Brain Inj. 9, 213–219.Google Scholar
Mortimer, J.A., van Duijn, C.M., Chandra, V., Fratiglioni, L., Graves, A.B., Heyman, A., Jorm, A.F., Kokmen, E., Kondo, K., Rocca, W.A., Shalat, S.L., Soininen, H., Hofman, A., 1991. Head trauma as a risk factor for Alzheimer’s disease: a collaborative re-analysis of case–control studies. EURODEM Risk Factors Research Group. Int. J. Epidemiol. 20 (Suppl. 2), S28–S35.CrossRefGoogle ScholarPubMed
Fleminger, S., Oliver, D.L., Lovestone, S., Rabe-Hesketh, S., Giora, A., 2003. Head injury as a risk factor for Alzheimer’s disease: the evidence 10 years on; a partial replication. J. Neurol. Neurosurg. Psychiatry 74, 857–862.CrossRefGoogle ScholarPubMed
Bachman, D.L., Wolf, P.A., Linn, R., Knoefel, J.E., Cobb, J., Belanger, A., D’Agostino, R.B., White, L.R., 1992. Prevalence of dementia and probable senile dementia of the Alzheimer type in the Framingham Study. Neurology 42, 115–119.CrossRefGoogle ScholarPubMed
Plassman, B.L., Havlik, R.J., Steffens, D.C., Helms, M.J., Newman, T.N., Drosdick, D., Phillips, C., Gau, B.A., Welsh-Bohmer, K.A., Burke, J.R., Guralnik, J.M., Breitner, J.C., 2000. Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias. Neurology 55, 1158–1166.CrossRefGoogle ScholarPubMed
Gardner, R.C., Burke, J.F., Nettiksimmons, J., Kaup, A., Barnes, D.E., Yaffe, K., 2014. Dementia risk after traumatic brain injury vs nonbrain trauma: the role of age and severity. JAMA Neurol. 71, 1490–1497.Google Scholar
Rosso, S.M., Landweer, E.J., Houterman, M., Donker Kaat, L., van Duijn, C.M., van Swieten, J.C., 2003. Medical and environmental risk factors for sporadic frontotemporal dementia: a retrospective case–control study. J. Neurol. Neurosurg. Psychiatry 74, 1574–1576.Google Scholar
Kalkonde, Y.V., Jawaid, A., Qureshi, S.U., Shirani, P., Wheaton, M., Pinto-Patarroyo, G.P., Schulz, P.E., 2012. Medical and environmental risk factors associated with frontotemporal dementia: a case–control study in a veteran population. Alzheimers Dement. 8, 204–210.Google Scholar
Wang, H.K., Lee, Y.C., Huang, C.Y., Liliang, P.C., Lu, K., Chen, H.J., Li, Y.C., Tsai, K.J., 2015. Traumatic brain injury causes frontotemporal dementia and TDP-43 proteolysis. Neuroscience 14, 94–103.Google Scholar
Graves, A.B., White, E., Koepsell, T.D., Reifler, B.V., van Belle, G., Larson, E.B., Raskind, M., 1990. The association between head trauma and Alzheimer’s disease. Am. J. Epidemiol. 131, 491–501.Google Scholar
Corder, E.H., Saunders, A.M., Strittmatter, W.J., Schmechel, D.E., Gaskell, P.C., Small, G.W., Roses, A.D., Haines, J.L., Pericak-Vance, M.A., 1993. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families. Science 261, 921–923.Google Scholar
Mayeux, R., Ottman, R., Maestre, G., Ngai, C., Tang, M.X., Ginsberg, H., Chun, M., Tycko, B., Shelanski, M., 1995. Synergistic effects of traumatic head injury and apolipoproteinepsilon 4 in patients with Alzheimer’s disease. Neurology 45, 555–557.Google Scholar
Caamano-Isorna, F., Corral, M., Montes-Martinez, A., Takkouche, B., 2006. Education and dementia: a meta-analytic study. Neuroepidemiology 26, 226–232.Google Scholar
Raymont, V., Greathouse, A., Reding, K., Lipsky, R., Salazar, A., Grafman, J., 2008. Demographic, structural and genetic predictors of late cognitive decline after penetrating head injury. Brain 131, 543–558.CrossRefGoogle ScholarPubMed
Jafari, S., Etminan, M., Aminzadeh, F., Samii, A., 2013. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov. Disord. 28, 1222–1229.Google Scholar
Gardner, R.C., Burke, J.F., Nettiksimmons, J., Goldman, S., Tanner, C.M., Yaffe, K., 2015. Traumatic brain injury in later life increases risk for Parkinson disease. Ann. Neurol. 77, 987–995.CrossRefGoogle ScholarPubMed
Hardy, J., Selkoe, D.J., 2002. The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297, 353–356.Google Scholar
Polymeropoulos, M.H., Lavedan, C., Leroy, E., Ide, S.E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., Stenroos, E.S., Chandrasekharappa, S., Athanassiadou, A., Papapetropoulos, T., Johnson, W.G., Lazzarini, A.M., Duvoisin, R.C., Di Iorio, G., Golbe, L.I., Nussbaum, R.L., 1997. Mutation in the alpha-synuclein gene identified in families with Parkinson’s disease. Science 276, 2045–2047.Google Scholar
Neumann, M., Sampathu, D.M., Kwong, L.K., Truax, A.C., Micsenyi, M.C., Chou, T.T., Bruce, J., Schuck, T., Grossman, M., Clark, C.M., McCluskey, L.F., Miller, B.L., Masliah, E., Mackenzie, I.R., Feldman, H., Feiden, W., Kretzschmar, H.A., Trojanowski, J.Q., Lee, V.M., 2006. Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130–133.Google Scholar
Uryu, K., Chen, X.H., Martinez, D., Browne, K.D., Johnson, V.E., Graham, D.I., Lee, V.M., Trojanowski, J.Q., Smith, D.H., 2007. Multiple proteins implicated in neurodegenerative diseases accumulate in axons after brain trauma in humans. Exp. Neurol. 208, 185–192.Google Scholar
Johnson, V.E., Stewart, W., Smith, D.H., 2012. Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans. Brain Pathol. 22, 142–149.Google Scholar
Roberts, G.W., Gentleman, S.M., Lynch, A., Graham, D.I., 1991. Beta A4 amyloid protein deposition in brain after head trauma. Lancet 338, 1422–1423.Google Scholar
Braak, H., Braak, E., 1997. Diagnostic criteria for neuropathologic assessment of Alzheimer’s disease. Neurobiol. Aging 18, S85–S88.Google Scholar
Roberts, G.W., Gentleman, S.M., Lynch, A., Murray, L., Landon, M., Graham, D.I., 1994. Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer’s disease. J. Neurol. Neurosurg. Psychiatry 57, 419–425.Google Scholar
Ikonomovic, M.D., Uryu, K., Abrahamson, E.E., Ciallella, J.R., Trojanowski, J.Q., Lee, V.M., Clark, R.S., Marion, D.W.,Wisniewski, S.R., Dekosky, S.T., 2004. Alzheimer’s pathology in human temporal cortex surgically excised after severe brain injury. Exp. Neurol. 190, 192–203.Google Scholar
Wu, C., Pike, V.W., Wang, Y., 2005. Amyloid imaging: frombenchtop to bedside. Curr. Top. Dev. Biol. 70, 171–213.CrossRefGoogle Scholar
Hong, Y.T., Veenith, T., Dewar, D., Outtrim, J.G., Mani, V., Williams, C., Pimlott, S., Hutchinson, P.J., Tavares, A., Canales, R., Mathis, C.A., Klunk, W.E., Aigbirhio, F.I., Coles, J.P., Baron, J.C., Pickard, J.D., Fryer, T.D., Stewart, W., Menon, D.K., 2014. Amyloid imaging with carbon 11-labeled Pittsburgh compound B for traumatic brain injury. JAMA Neurol. 71, 23–31.Google Scholar
Smith, D.H., Chen, X.H., Iwata, A., Graham, D.I., 2003. Amyloid beta accumulation in axons after traumatic brain injury in humans. J. Neurosurg. 98, 1072–1077.Google Scholar
Chen, X.H., Johnson, V.E., Uryu, K., Trojanowski, J.Q., Smith, D.H., 2009. A lack of amyloid beta plaques despite persistent accumulation of amyloid beta in axons of long-term survivors of traumatic brain injury. Brain Pathol. 19, 214–223.Google Scholar
Gatson, J.W., Warren, V., Abdelfattah, K., Wolf, S., Hynan, L.S., Moore, C., Diaz-Arrastia, R., Minei, J.P., Madden, C., Wigginton, J.G., 2013. Detection of beta-amyloid oligomers as a predictor of neurological outcome after brain injury. J. Neurosurg. 118, 1336–1342.Google Scholar
Smith, D.H., Chen, X.H., Nonaka, M., Trojanowski, J.Q., Lee, V.M., Saatman, K.E., Leoni, M.J., Xu, B.N., Wolf, J.A., Meaney, D.F., 1999. Accumulation of amyloid beta and tau and the formation of neurofilament inclusions following diffuse brain injury in the pig. J. Neuropathol. Exp. Neurol. 58, 982–992.Google Scholar
Chen, X.H., Siman, R., Iwata, A., Meaney, D.F., Trojanowski, J.Q., Smith, D.H., 2004. Longterm accumulation of amyloid-beta, beta-secretase, presenilin-1, and caspase-3 in damaged axons following brain trauma. Am. J. Pathol. 165, 357–371.CrossRefGoogle ScholarPubMed
Conte, V., Uryu, K., Fujimoto, S., Yao, Y., Rokach, J., Longhi, L., Trojanowski, J.Q., Lee, V.M., McIntosh, T.K., Pratico, D., 2004. Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury. J. Neurochem. 90, 758–764.Google Scholar
Abrahamson, E.E., Ikonomovic, M.D., Ciallella, J.R., Hope, C.E., Paljug, W.R., Isanski, B.A., Flood, D.G., Clark, R.S., DeKosky, S.T., 2006. Caspase inhibition therapy abolishes brain trauma-induced increases in Abeta peptide: implications for clinical outcome. Exp. Neurol. 197, 437–450.Google Scholar
Abrahamson, E.E., Ikonomovic, M.D., Dixon, C.E., Dekosky, S.T., 2009. Simvastatin therapy prevents brain trauma-induced increases in beta-amyloid peptide levels. Ann. Neurol. 66, 407–414.Google Scholar
Loane, D.J., Pocivavsek, A., Moussa, C.E., Thompson, R., Matsuoka, Y., Faden, A.I., Rebeck, G.W., Burns, M.P., 2009. Amyloid precursor protein secretases as therapeutic targets for traumatic brain injury. Nat. Med. 15, 377–379.Google Scholar
Laskowitz, D.T., Song, P., Wang, H., Mace, B., Sullivan, P.M., Vitek, M.P., Dawson, H.N., 2010. Traumatic brain injury exacerbates neurodegenerative pathology: improvement with an apolipoprotein E-based therapeutic. J. Neurotrauma 27, 1983–1995.Google Scholar
Tran, H.T., LaFerla, F.M., Holtzman, D.M., Brody, D.L., 2011. Controlled cortical impact traumatic brain injury in 3xTg-AD mice causes acute intra-axonal amyloid-beta accumulation and independently accelerates the development of tau abnormalities. J. Neurosci. Off. J. Soc. Neurosci. 31, 9513–9525.CrossRefGoogle ScholarPubMed
Washington, P.M., Morffy, N., Parsadanian, M., Zapple, D.N., Burns, M.P., 2014. Experimental traumatic brain injury induces rapid aggregation and oligomerization of amyloidbeta in an Alzheimer’s disease mouse model. J. Neurotrauma 31, 125–134.Google Scholar
Tran, H.T., Sanchez, L., Esparza, T.J., Brody, D.L., 2011. Distinct temporal and anatomical distributions of amyloid-beta and tau abnormalities following controlled cortical impact in transgenic mice. PLoS One 6, e25475.Google Scholar
Winston, C.N., Chellappa, D., Wilkins, T., Barton, D.J., Washington, P.M., Loane, D.J., Zapple, D.N., Burns, M.P., 2013. Controlled cortical impact results in an extensive loss of dendritic spines that is not mediated by injury-induced amyloid-beta accumulation. J. Neurotrauma 30, 1966–1972.Google Scholar
Iwata, N., Tsubuki, S., Takaki, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., Kawashima-Morishima, M., Lee, H.J., Hama, E., Sekine-Aizawa, Y., Saido, T.C., 2000. Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat. Med. 6, 143–150.Google Scholar
Johnson, V.E., Stewart, W., Graham, D.I., Stewart, J.E., Praestgaard, A.H., Smith, D.H., 2009. A neprilysin polymorphism and amyloid-beta plaques after traumatic brain injury. J. Neurotrauma 26, 1197–1202.Google Scholar
Kokjohn, T.A., Maarouf, C.L., Daugs, I.D., Hunter, J.M., Whiteside, C.M., Malek-Ahmadi, M., Rodriguez, E., Kalback, W., Jacobson, S.A., Sabbagh, M.N., Beach, T.G., Roher, A.E., 2013. Neurochemical profile of dementia pugilistica. J. Neurotrauma 30, 981–997.Google Scholar
Deane, R., Sagare, A., Hamm, K., Parisi, M., Lane, S., Finn, M.B., Holtzman, D.M., Zlokovic, B.V., 2008. apoE isoform-specific disruption of amyloid beta peptide clearance from mouse brain. J. Clin. Invest. 118, 4002–4013.CrossRefGoogle ScholarPubMed
Jiang, Q., Lee, C.Y., Mandrekar, S., Wilkinson, B., Cramer, P., Zelcer, , Richardson, J.C., Smith, J.D., Comery, T.A., Riddell, D., Holtzman, , et al., 2008. ApoE promotes the proteolytic degradation of Abeta. Neuron 58, 681–693.Google Scholar
Nicoll, J.A., Roberts, G.W., Graham, D.I., 1995. Apolipoprotein E epsilon 4 allele is associated with deposition of amyloid beta-protein following head injury. Nat. Med. 1, 135–137.Google Scholar
Hartman, R.E., Laurer, H., Longhi, L., Bales, K.R., Paul, S.M., McIntosh, T.K., Holtzman, D.M., 2002. Apolipoprotein E4 influences amyloid deposition but not cell loss after traumatic brain injury in a mouse model of Alzheimer’s disease. J. Neurosci. 22, 10083–10087.Google Scholar
Gentleman, S.M., Greenberg, B.D., Savage, M.J., Noori, M., Newman, S.J., Roberts, G.W., Griffin, W.S., et al. 1997. A beta 42 is the predominant form of amyloid beta-protein in the brains of short-term survivors of head injury. Neuroreport 8, 1519–1522.Google Scholar
Smith, C., Graham, D.I., Murray, L.S., Nicoll, J.A., 2003. Tau immunohistochemistry in acute brain injury. Neuropathol. Appl. Neurobiol. 29, 496–502.Google Scholar
Constantinidis, J., Tissot, R., 1967. Generalized Alzheimer’s neurofibrillary lesions without senile plaques (presentation of one anatomo-clinical case). Schweiz. Arch. Neurol. Neurochir. Psychiatr. 100, 117–130.Google Scholar
Corsellis, J.A., Bruton, C.J., Freeman-Browne, D., 1973. The aftermath of boxing. Psychol. Med. 3, 270–303.Google Scholar
Allsop, D., Haga, S., Bruton, C., Ishii, T., Roberts, G.W., 1990. Neurofibrillary tangles in some cases of dementia pugilistica share antigens with amyloid beta-protein of Alzheimer’s disease. Am. J. Pathol. 136, 255–260.Google Scholar
Dale, G.E., Leigh, P.N., Luthert, P., Anderton, B.H., Roberts, G.W., 1991. Neurofibrillary tangles in dementia pugilistica are ubiquitinated. J. Neurol. Neurosurg. Psychiatry 54, 116–118.CrossRefGoogle ScholarPubMed
Tokuda, T., Ikeda, S., Yanagisawa, N., Ihara, Y., Glenner, G.G., 1991. Re-examination of exboxers’ brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. Acta Neuropathol. 82, 280–285.Google Scholar
Hof, P.R., Bouras, C., Buee, L., Delacourte, A., Perl, D.P., Morrison, J.H., 1992. Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer’s disease cases. Acta Neuropathol. 85, 23–30.Google Scholar
Geddes, J.F., Vowles, G.H., Robinson, S.F., Sutcliffe, J.C., 1996. Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol. Appl. Neurobiol. 22, 12–16.Google Scholar
Geddes, J.F., Vowles, G.H., Nicoll, J.A., Revesz, T., 1999. Neuronal cytoskeletal changes are an early consequence of repetitive head injury. Acta Neuropathol. 98, 171–178.Google Scholar
Schmidt, M.L., Zhukareva, V., Newell, K.L., Lee, V.M., Trojanowski, J.Q., 2001. Tau isoform profile and phosphorylation state in dementia pugilistica recapitulate Alzheimer’s disease. Acta Neuropathol. 101, 518–524.Google Scholar
Areza-Fegyveres, R., Rosemberg, S., Castro, R.M., Porto, C.S., Bahia, V.S., Caramelli, P., Nitrini, R., 2007. Dementia pugilistica with clinical features of Alzheimer’s disease. Arq. Neuropsiquiatr. 65, 830–833.Google Scholar
McKee, A.C., Cantu, R.C., Nowinski, C.J., Hedley-Whyte, E.T., Gavett, B.E., Budson, A.E., Santini, V.E., Lee, H.S., Kubilus, C.A., Stern, R.A., 2009. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J. Neuropathol. Exp. Neurol. 68, 709–735.Google Scholar
Saing, T., Dick, M., Nelson, P.T., Kim, R.C., Cribbs, D.H., Head, E., 2012. Frontal cortex neuropathology in dementia pugilistica. J. Neurotrauma 29, 1054–1070.Google Scholar
McKee, A.C., Stein, T.D., Kiernan, P.T., Alvarez, V.E., 2015. The neuropathology of chronic traumatic encephalopathy. Brain Pathol. 25, 350–364.Google Scholar
Omalu, B., Bailes, J., Hamilton, R.L., Kamboh, M.I., Hammers, J., Case, M., Fitzsimmons, R., 2011. Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 69, 173–183 (discussion 183).CrossRefGoogle ScholarPubMed
Goldstein, L.E., Fisher, A.M., Tagge, C.A., Zhang, X.-L., Velisek, L., Sullivan, , et al., 2012. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci. Transl. Med. 4, 134ra160.Google Scholar
Stein, T.D., Montenigro, P.H., Alvarez, V.E., Xia, W., Crary, J.F., Tripodis, , et al., 2015. Beta-amyloid deposition in chronic traumatic encephalopathy. Acta Neuropathol. 130, 21–34.Google Scholar
Namjoshi, D.R., Cheng, W.H., McInnes, K.A., Martens, K.M., Carr, M., Wilkinson, A., et al., 2014. Merging pathology with biomechanics using CHIMERA (Closed-Head Impact Model of Engineered Rotational Acceleration): a novel, surgery-free model of traumatic brain injury. Mol. Neurodegener. 9, 55.Google Scholar
Yoshiyama, Y., Uryu, K., Higuchi, M., Longhi, L., Hoover, R., Fujimoto, S., et al., 2005. Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model. J. Neurotrauma 22, 1134–1141.Google Scholar
Ojo, J.O., Mouzon, B., Greenberg, M.B., Bachmeier, C., Mullan, M., Crawford, F., 2013. Repetitive mild traumatic brain injury augments tau pathology and glial activation in aged hTau mice. J. Neuropathol. Exp. Neurol. 72, 137–151.Google Scholar
Newell, K.L., Boyer, P., Gomez-Tortosa, E., Hobbs, W., Hedley-Whyte, E.T., Vonsattel, J.P., et al., 1999. Alpha-synuclein immunoreactivity is present in axonal swellings in neuroaxonal dystrophy and acute traumatic brain injury. J. Neuropathol. Exp. Neurol. 58, 1263–1268.CrossRefGoogle ScholarPubMed
Johnson, V.E., Stewart, W., Trojanowski, J.Q., Smith, D.H., 2011. Acute and chronically increased immunoreactivity to phosphorylation-independent but not pathological TDP-43 after a single traumatic brain injury in humans. Acta Neuropathol. 122, 715–726.Google Scholar

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