TDP-43 proteinopathy and motor neuron disease in chronic traumatic encephalopathy
Open accessAbstract
Epidemiological evidence suggests that the incidence of amyotrophic lateral sclerosis is increased in association with head injury. Repetitive head injury is also associated with the development of chronic traumatic encephalopathy (CTE), a tauopathy characterized by neurofibrillary tangles throughout the brain in the relative absence of β-amyloid deposits. We examined 12 cases of CTE and, in 10, found a widespread TAR DNA-binding protein of approximately 43kd (TDP-43) proteinopathy affecting the frontal and temporal cortices, medial temporal lobe, basal ganglia, diencephalon, and brainstem. Three athletes with CTE also developed a progressive motor neuron disease with profound weakness, atrophy, spasticity, and fasciculations several years before death. In these 3 cases, there were abundant TDP-43-positive inclusions and neurites in the spinal cord in addition to tau neurofibrillary changes, motor neuron loss, and corticospinal tract degeneration. The TDP-43 proteinopathy associated with CTE is similar to that found in frontotemporal lobar degeneration with TDP-43 inclusions, in that widespread regions of the brain are affected. Akin to frontotemporal lobar degeneration with TDP-43 inclusions, in some individuals with CTE, the TDP-43 proteinopathy extends to involve the spinal cord and is associated with motor neuron disease. This is the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.
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It is well established that a large percentage of former athletes identified as having CTE neuropathology also have neuropathology associated with age related neurodegenerative diseases such as AD, PD, Lewy body disease, hippocampal sclerosis, and ALS to the extent that they meet full neuropathological criteria for an alternative, well-characterized neurodegenerative disease.
“It is now well established that a large percentage of former athletes identified as having CTE neuropathology also have neuropathology associated with age related neurodegenerative diseases such as AD, PD, Lewy body disease, hippocampal sclerosis, and ALS [14, 41–44] to the extent that they meet full neuropathological criteria for an alternative, well-characterized neurodegenerative disease [16].”
From The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features (2017) · cites this paper as [43]
In 2013, the largest single cohort of neuropathologically confirmed cases of CTE was reported.
“In 2013, the largest single cohort of neuropathologically confirmed cases of CTE was reported [127]”
From The neuropathology of sport (2014) · cites this paper as [127]
CTE is associated with the development of other neurodegenerations, notably Lewy body disease, AD, frontotemporal lobar degeneration, and motor neuron disease.
“CTE is associated with the development of other neurode-generations, notably Lewy body disease (LBD), AD, fron-totemporal lobar degeneration (FTLD), and motor neuron disease (MND) [127, 128].”
From The neuropathology of sport (2014) · cites this paper as [127]
CTE has been diagnosed neuropathologically in American football players, professional and amateur boxers, ice hockey players, professional wrestlers, soccer players, rugby players, and a professional baseball player.
“Although CTE was first identified in association with boxing, CTE has been diagnosed neuropathologically in American football players, professional and amateur boxers, ice hockey players, professional wrestlers, soccer players, rugby players, and a professional baseball player (Figs. 3, 4, 5, 6) [38, 65, 66, 88, 91, 127, 128, 146–148].”
From The neuropathology of sport (2014) · cites this paper as [127]
Either repetitive trauma or the accumulation of tau pathology in CTE provokes the deposition of other abnormal proteins involved in neurodegeneration.
“In our current experience of 103 neuropathologically confirmed cases of CTE, co-existent LBD was found in 12 (12 %) cases, MND in 13 (13 %), AD in 15 (15 %), and FTLD in 6 (6 %), suggesting that either repetitive trauma or the accumulation of tau pathology in CTE provokes the deposition of other abnormal proteins involved in neurodegeneration [127, 128].”
From The neuropathology of sport (2014) · cites this paper as [127]
In our current experience of 103 neuropathologically confirmed cases of CTE, co-existent LBD was found in 12 (12%) cases, MND in 13 (13%), AD in 15 (15%), and FTLD in 6 (6%).
“In our current experience of 103 neuropathologically confirmed cases of CTE, co-existent LBD was found in 12 (12 %) cases, MND in 13 (13 %), AD in 15 (15 %), and FTLD in 6 (6 %), suggesting that either repetitive trauma or the accumulation of tau pathology in CTE provokes the deposition of other abnormal proteins involved in neurodegeneration [127, 128].”
From The neuropathology of sport (2014) · cites this paper as [127]
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Cites
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
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., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576 · see citing works
Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.093 · Cited by 2,732 · see citing works
Chronic traumatic encephalopathy in athletes: Progressive tauopathy after repetitive head injury
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) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181a9d503 · Cited by 2,295 · see citing works
Self-citationUNRAVELING THE MECHANISMS INVOLVED IN MOTOR NEURON DEGENERATION IN ALS
Bruijn, L. I., Miller, T. M., & Cleveland, D. W. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144244 · Cited by 1,371 · see citing works
Cairns, N. J., Bigio, E. H., Mackenzie, I. R. A., Neumann, M., Lee, V. M.-Y., Hatanpaa, K. J., White, C. L., Schneider, J. A., Grinberg, L. T., Halliday, G., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0237-2 · Cited by 1,110 · see citing works
TDP‐43 immunoreactivity in hippocampal sclerosis and Alzheimer's disease
Amador‐Ortiz, C., Lin, W., Ahmed, Z., Personett, D., Davies, P., Duara, R., Graff‐Radford, N. R., Hutton, M. L., & Dickson, D. W. (2007) · Annals of Neurology · doi:10.1002/ana.21154 · Cited by 916 · see citing works
Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias
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., et al. (2000) · Neurology · doi:10.1212/wnl.55.8.1158 · Cited by 896 · see citing works
Fleminger, S. (2003) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.7.857 · Cited by 719 · see citing works
Mayeux, R., Ottman, R., Maestre, G., Ngai, C., Tang, M., Ginsberg, H., Chun, M., Tycko, B., & Shelanski, M. (1995) · Neurology · doi:10.1212/wnl.45.3.555 · Cited by 597 · see citing works
Wils, H., Kleinberger, G., Janssens, J., Pereson, S., Joris, G., Cuijt, I., Smits, V., Groote, C. C., Broeckhoven, C. V., & Kumar‐Singh, S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912417107 · Cited by 592 · see citing works
Barmada, S. J., Skibinski, G., Korb, E., Rao, E. J., Wu, J. Y., & Finkbeiner, S. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4988-09.2010 · Cited by 554 · see citing works
Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players
Chio, A. (2005) · Brain · doi:10.1093/brain/awh373 · Cited by 484 · see citing works
Co-morbidity of TDP-43 proteinopathy in Lewy body related diseases
Nakashima-Yasuda, H., Uryu, K., Robinson, J., Xie, S. X., Hurtig, H., Duda, J. E., Arnold, S. E., Siderowf, A., Grossman, M., Leverenz, J. B., et al. (2007) · Acta Neuropathologica · doi:10.1007/s00401-007-0261-2 · Cited by 468 · see citing works
Familial adult motor neuron disease: amyotrophic lateralsclerosis
Mulder, D. W., Kurland, L. T., Offord, K. P., & Beard, C. M. (1986) · Neurology · doi:10.1212/wnl.36.4.511 · Cited by 400 · see citing works
Uryu, K., Chen, X.-H., Martinez, D., Browne, K. D., Johnson, V. E., Graham, D. I., Lee, V. M.-Y., Trojanowski, J. Q., & Smith, D. H. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.06.018 · Cited by 360 · see citing works
TDP43 is a human low molecular weight neurofilament (hNFL) mRNA-binding protein
Strong, M. J., Volkening, K., Hammond, R. R., Yang, W., Strong, W., Leystra‐Lantz, C., & Shoesmith, C. L. (2007) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2007.03.007 · Cited by 349 · see citing works
Mackenzie, I. R., Baborie, A., Pickering-Brown, S. M., du Plessis, D., Jaros, E., Perry, R. H., Neary, D., Snowden, J. S., & Mann, D. M. A. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0138-9 · Cited by 322 · see citing works
Sampathu, D. M., Neumann, M., Kwong, L. K., Chou, T. T. T., Micsenyi, M. C., Truax, A. C., BRUCE, J. S., Grossman, M., Trojanowski, J. Q., & Lee, V. M. ‐. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.060438 · Cited by 317 · see citing works
Head injury as a risk factor for Alzheimer's disease
Mortimer, J. A., French, L., Hutton, J. T., & Schuman, L. M. (1985) · Neurology · doi:10.1212/wnl.35.2.264 · Cited by 308 · see citing works
Head injury and Parkinson's disease risk in twins
Goldman, S. M., Tanner, C. M., Oakes, D., Bhudhikanok, G. S., Gupta, A., & Langston, J. W. (2006) · Annals of Neurology · doi:10.1002/ana.20882 · Cited by 289 · see citing works
Head Injury and Amyotrophic Lateral Sclerosis
Chen, H., Richard, M., Sandler, D. P., Umbach, D. M., & Kamel, F. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwm153 · Cited by 279 · see citing works
Occurrence of amyotrophic lateral sclerosis among Gulf War veterans
Horner, R. D., Kamins, K. G., Feussner, J. R., Grambow, S. C., Lindquist, J. H., Harati, Y., Mitsumoto, H., Pascuzzi, R. M., Spencer, P. S., Tim, R., et al. (2003) · Neurology · doi:10.1212/01.wnl.0000069922.32557.ca · Cited by 276 · see citing works
Clinical and Pathological Continuum of Multisystem TDP-43 Proteinopathies
Geser, F., Martinez-Lage, M., Robinson, J., Uryu, K., Neumann, M., Brandmeir, N. J., Xie, S. X., Kwong, L. K., Elman, L., McCluskey, L., et al. (2009) · Archives of Neurology · doi:10.1001/archneurol.2008.558 · Cited by 267 · see citing works
Head trauma and risk of dementia and Alzheimer’s disease
Mehta, K. M., Ott, A., Kalmijn, S., Slooter, A. J. C., van Duijn, C. M., Albert Hofman, D., & Breteler, M. M. B. (1999) · Neurology · doi:10.1212/wnl.53.9.1959 · Cited by 245 · see citing works
TDP-43 is deposited in the Guam parkinsonism-dementia complex brains
Hasegawa, M., Arai, T., Akiyama, H., Nonaka, T., Mori, H., Hashimoto, T., Yamazaki, M., & Oyanagi, K. (2007) · Brain · doi:10.1093/brain/awm065 · Cited by 242 · see citing works
Premorbid weight, body mass, and varsity athletics in ALS
Scarmeas, N., Shih, T., Stern, Y., Ottman, R., & Rowland, L. P. (2002) · Neurology · doi:10.1212/wnl.59.5.773 · Cited by 235 · see citing works
Occupational Exposures and Amyotrophic Lateral Sclerosis. A Population-based Case-Control Study
McGuire, V. M., Longstreth, W. T., Jr., Nelson, L. M., Koepsell, T. D., Checkoway, H., Morgan, M. S., & van Belle, G. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009070 · Cited by 235 · see citing works
Wightman, G., Anderson, V., Martin, J., Swash, M., Anderton, B. H., Neary, D., Mann, D. M. A., Luthert, P. J., & Leigh, P. N. (1992) · Neuroscience Letters · doi:10.1016/0304-3940(92)90569-s · Cited by 233 · see citing works
Occurrence of amyotrophic lateral sclerosis among Gulf War veterans
Armon, C. (2007) · Neurology · doi:10.1212/01.wnl.0000260429.80237.c0 · Cited by 224 · see citing works
Excess incidence of ALS in young Gulf War veterans
Haley, R. W. (2003) · Neurology · doi:10.1212/wnl.61.6.750 · Cited by 223 · see citing works
Bower, J. H., Maraganore, D. M., Peterson, B. J., McDonnell, S. K., Ahlskog, J. E., & Rocca, W. A. (2003) · Neurology · doi:10.1212/01.wnl.0000068008.78394.2c · Cited by 206 · see citing works
Prospective study of military service and mortality from ALS
Weisskopf, M. G., O’Reilly, É. J., McCullough, M. L., Calle, E. E., Thun, M. J., Cudkowicz, M., & Ascherio, A. (2005) · Neurology · doi:10.1212/01.wnl.0000148649.17706.d9 · Cited by 194 · see citing works
Amyotrophic lateral sclerosis, frontotemporal dementia and beyond: the TDP-43 diseases
Geser, F., Martinez‐Lage, M., Kwong, L. K., Lee, V. M. ‐., & Trojanowski, J. Q. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5069-7 · Cited by 190 · see citing works
A CASE-CONTROL STUDY OF AMYOTROPHIC LATERAL SCLEROSIS1
Deapen, D., & Henderson, B. E. (1986) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a114308 · Cited by 184 · see citing works
Lead Exposure and Amyotrophic Lateral Sclerosis
Kamel, F., Umbach, D. M., Munsat, T. L., Shefner, J. M., Hu, H., & Sandler, D. P. (2002) · Epidemiology · doi:10.1097/00001648-200205000-00012 · Cited by 170 · see citing works
Nelson, L. M., McGuire, V. M., Longstreth, W. T., Jr., & Matkin, C. C. (2000) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a010183 · Cited by 168 · see citing works
Epidemiology of amyotrophic lateral sclerosis.
Kurtzke, J. F. (1982) · PubMed · Cited by 165 · see citing works
Head Injury and Risk of Alzheimer's Disease by Apolipoprotein E Genotype
O’Meara, E. S., Kukull, W. A., Sheppard, L. A., Bowen, J., McCormick, W. C., Teri, L. L., Pfanschmidt, M. L., Thompson, J. D., Schellenberg, G. D., & Larson, E. B. (1997) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a009290 · Cited by 165 · see citing works
Prospective Study of Cigarette Smoking and Amyotrophic Lateral Sclerosis
Weisskopf, M. G. (2004) · American Journal of Epidemiology · doi:10.1093/aje/kwh179 · Cited by 149 · see citing works
Genetic epidemiology of amyotrophic lateral sclerosis
Majoor‐Krakauer, D., Willems, P., & Hofman, A. (2003) · Clinical Genetics · doi:10.1046/j.0009-9163.2002.00001.x · Cited by 147 · see citing works
Nelson, L. M., Matkin, C. C., Longstreth, W. T., Jr., & McGuire, V. M. (2000) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a010184 · Cited by 144 · see citing works
Belli, S., & Vanacore, N. (2005) · European Journal of Epidemiology · doi:10.1007/s10654-004-6879-7 · Cited by 140 · see citing works
Chancellor, A. M., Slattery, J. M. A., Fraser, H., & Warlow, C. P. (1993) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.56.11.1200 · Cited by 138 · see citing works
Epidemiology of amyotrophic lateral sclerosis
Kurtzke, J. F., & Beebe, G. W. (1980) · Neurology · doi:10.1212/wnl.30.5.453 · Cited by 136 · see citing works
Antecedent events in amyotrophic lateral sclerosis
Felmus, M. T., Patten, B. M., & Swanke, L. (1976) · Neurology · doi:10.1212/wnl.26.2.167 · Cited by 134 · see citing works
Temporal lobar predominance of TDP-43 neuronal cytoplasmic inclusions in Alzheimer disease
Hu, W. T., Josephs, K. A., Knopman, D. S., Boeve, B. F., Dickson, D. W., Petersen, R. C., & Parisi, J. E. (2008) · Acta Neuropathologica · doi:10.1007/s00401-008-0400-4 · Cited by 134 · see citing works
An Improved Approach to Prepare Human Brains for Research
Vonsattel, J. P., Aizawa, H., DiFiglia, M., McKee, A. C., MacDonald, M. E., Gusella, J. F., Landwehrmeyer, G. B., Bird, E. D., Richardson, E. P., & Hedley‐Whyte, E. T. (1995) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199501000-00006 · Cited by 134 · see citing works
Self-citationMotor neurone disease and exposure to lead
Campbell, A. M. G., Williams, E. R., & BARLTROP, D. (1970) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.33.6.877 · Cited by 127 · see citing works
Okamoto, K., Murakami, N., Kusaka, H., Yoshida, M., Hashizume, Y., Nakazato, Y., Matsubara, E., & Hirai, S. (1992) · Journal of Neurology · doi:10.1007/bf00856806 · Cited by 122 · see citing works
King, A., Sweeney, F., Bódi, I., Troakes, C., Maekawa, S., & Al‐Sarraj, S. (2010) · Neuropathology · doi:10.1111/j.1440-1789.2009.01085.x · Cited by 118 · see citing works
Neuropathology of non-Alzheimer degenerative disorders.
(2009) · PubMed Central · Cited by 117 · see citing works
Association of ALS with head injury, cigarette smoking and APOE genotypes
Schmidt, S., Kwee, L. C., Allen, K. D., & Oddone, E. Z. (2010) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2010.01.011 · Cited by 117 · see citing works
Physical activity, trauma, and ALS: a case-control study
Strickland, D., Smith, S. A., Dolliff, G., Goldman, L., & Roelofs, R. I. (1996) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1996.tb00038.x · Cited by 115 · see citing works
Case-Control Studies of Motor Neuron Disease
Kondo, K. (1981) · Archives of Neurology · doi:10.1001/archneur.1981.00510040046007 · Cited by 112 · see citing works
Risk of Amyotrophic Lateral Sclerosis and History of Physical Activity
Longstreth, W. T., Jr., McGuire, V. M., Koepsell, T. D., Wang, Y., & van Belle, G. (1998) · Archives of Neurology · doi:10.1001/archneur.55.2.201 · Cited by 110 · see citing works
Epidemiologic correlates of sporadic amyotrophic lateral sclerosis
Armon, C., Kurland, L. T., Daube, J. R., & O’Brien, P. C. (1991) · Neurology · doi:10.1212/wnl.41.7.1077 · Cited by 102 · see citing works
Football Increases the Risk for Lou Gehrig's Disease, Amyotrophic Lateral Sclerosis
Abel, E. L. (2007) · Perceptual and Motor Skills · doi:10.2466/pms.104.4.1251-1254 · Cited by 98 · see citing works
Association of Cigarette Smoking with Amyotrophic Lateral Sclerosis
Kamel, F., Umbach, D. M., Munsat, T. L., Shefner, J. M., & Sandler, D. P. (1999) · Neuroepidemiology · doi:10.1159/000026211 · Cited by 98 · see citing works
Moisse, K., Mepham, J., Volkening, K., Welch, I., Hill, T., & Strong, M. J. (2009) · Brain Research · doi:10.1016/j.brainres.2009.07.023 · Cited by 93 · see citing works
Temporal Profiles of Cytoskeletal Protein Loss following Traumatic Axonal Injury in Mice
Serbest, G., Burkhardt, M. F., Siman, R., et al. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9318-9 · Cited by 83 · see citing works
Tatom, J. B., Wang, D. B., Dayton, R. D., Skalli, O., Hutton, M. L., Dickson, D. W., & Klein, R. L. (2009) · Molecular Therapy · doi:10.1038/mt.2009.3 · Cited by 78 · see citing works
Amyotrophic Lateral Sclerosis and Occupational Heavy Metal Exposure: A Case-Control Study
Gresham, L. S., Molgaard, C. A., Golbeck, A. L., & Smith, R. A. (1986) · Neuroepidemiology · doi:10.1159/000110810 · Cited by 76 · see citing works
A Case-Control Study of Amyotrophic Lateral Sclerosis
Savettieri, G., Salemi, G., Arcara, A., Cassata, M., Castiglione, M. G., & Fierro, B. (1991) · Neuroepidemiology · doi:10.1159/000110279 · Cited by 66 · see citing works
Coffman, C. J., Horner, R. D., Grambow, S. C., et al. (2005) · Neuroepidemiology · doi:10.1159/000083297 · Cited by 62 · see citing works
Apolipoprotein-epsilon4 and head trauma: Synergistic or additive risks?
Katzman, R., Galasko, D. R., Saitoh, T., Chen, X., Pay, M. M., Booth, A., & Rg, T. (1996) · PubMed · Cited by 61 · see citing works
Repeat study of antecedent events in motor neuron disease.
Pierce‐Ruhland, R., & Bm, P. (1981) · PubMed · Cited by 57 · see citing works
Antecedent events in motor neuron disease.
Gawel, M. J., Zaiwalla, Z., & Rose, F. C. (1983) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.46.11.1041 · Cited by 57 · see citing works
Spinal Cord Neurofibrillary Pathology in Alzheimer Disease and Guam Parkinsonism-Dementia Complex
Schmidt, M. L., Zhukareva, V. A., Perl, D. P., Sheridan, S. K., Schuck, T., Lee, V. M. ‐., & Trojanowski, J. Q. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.11.1075 · Cited by 55 · see citing works
Self-citationBinazzi, A., Belli, S., Uccelli, R., Desiato, M. T., Talamanca, I. F., Antonini, G., Corsi, F. M., Scoppetta, C., Inghilleri, M., Pontieri, F. E., et al. (2009) · Amyotrophic Lateral Sclerosis · doi:10.3109/17482960802382313 · Cited by 46 · see citing works
Al‐Chalabi, A. (2005) · Brain · doi:10.1093/brain/awh426 · Cited by 42 · see citing works
Sieh, W., Choi, Y., Chapman, N. H., Craig, U.-K., Steinbart, E. J., Rothstein, J. H., Oyanagi, K., Garruto, R. M., Bird, T. D., Galasko, D. R., et al. (2009) · Human Molecular Genetics · doi:10.1093/hmg/ddp300 · Cited by 39 · see citing works
Zur Casuistik der bulbären Lähmungen
Erb, W. (1879) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/bf02666475 · Cited by 39 · see citing works
A Search for Clues to the Cause of Amyotrophic Lateral Sclerosis
Hanisch, R., Dworsky, R., & Henderson, B. E. (1976) · Archives of Neurology · doi:10.1001/archneur.1976.00500060062015 · Cited by 25 · see citing works
Zusammenhang der amyotrophischen Lateralsklerose mit gehäuften Elektrotraumata
Haynal, A., & Regli, F. (2007) · Confinia Neurologica · doi:10.1159/000104117 · Cited by 19 · see citing works
Umahara, T., Hirano, A., Kato, S., Shibata, N., & Yen, S. H. (1994) · Acta Neuropathologica · doi:10.1007/bf00294512 · Cited by 16 · see citing works
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The spectrum of disease in chronic traumatic encephalopathy
McKee, A. C., Stein, T. D., Nowinski, C. J., Stern, R. A., Daneshvar, D. H., Alvarez, V. E., Lee, H.-S., Hall, G., Wojtowicz, S. M., Baugh, C. M., et al. (2013) · Brain · doi:10.1093/brain/aws307 · Cited by 2,098 · see citing works
Self-citationThe far-reaching scope of neuroinflammation after traumatic brain injury
Simon, D. W., McGeachy, M. J., Bayır, H., Clark, R. S. B., Loane, D. J., & Kochanek, P. M. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.13 · Cited by 1,190 · see citing works
Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football
Mez, J., Daneshvar, D. H., Kiernan, P. T., Abdolmohammadi, B., Alvarez, V. E., Huber, B. R., Alosco, M. L., Solomon, T. M., Nowinski, C. J., McHale, L., et al. (2017) · JAMA · doi:10.1001/jama.2017.8334 · Cited by 1,098 · see citing works
Self-citationGoldstein, L. E., Fisher, A. M., Tagge, C. A., Zhang, X.-L., Velisek, L., Sullivan, J. A., Upreti, C., Kracht, J. M., Ericsson, M., Wojnarowicz, M. W., et al. (2012) · Science Translational Medicine · doi:10.1126/scitranslmed.3003716 · Cited by 958 · see citing works
Self-citationthe TBI/CTE group, McKee, A. C., Cairns, N. J., Dickson, D. W., Folkerth, R. D., Dirk Keene, C., Litvan, I., Perl, D. P., Stein, T. D., Vonsattel, J.-P., et al. (2016) · Acta Neuropathologica · doi:10.1007/s00401-015-1515-z · Cited by 885 · see citing works
Self-citationChronic neuropathologies of single and repetitive TBI: substrates of dementia?
Smith, D. H., Johnson, V. E., & Stewart, W. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.29 · Cited by 699 · see citing works
Gavett, B. E., Stern, R. A., & McKee, A. C. (2011) · Clinics in Sports Medicine · doi:10.1016/j.csm.2010.09.007 · Cited by 696 · see citing works
Self-citationThe Neuropathology and Neurobiology of Traumatic Brain Injury
Blennow, K., Hardy, J., & Zetterberg, H. (2012) · Neuron · doi:10.1016/j.neuron.2012.11.021 · Cited by 669 · see citing works
Epidemiology of mild traumatic brain injury and neurodegenerative disease
Gardner, R. C., & Yaffe, K. (2015) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2015.03.001 · Cited by 673 · see citing works
Arendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609 · see citing works
Neurodegenerative causes of death among retired National Football League players
Lehman, E. J., Hein, M. J., Baron, S. L., & Gersic, C. M. (2012) · Neurology · doi:10.1212/wnl.0b013e31826daf50 · Cited by 638 · see citing works
Widespread tau and amyloid-beta pathology many years after a single traumatic brain injury in humans
Johnson, V. E., Stewart, W., & Smith, D. H. (2012) · Brain Pathology · doi:10.1111/j.1750-3639.2011.00513.x · Cited by 620 · see citing works
Identification of common variants influencing risk of the tauopathy progressive supranuclear palsy
PSP Genetics Study Group, Höglinger, G. U., Melhem, N. M., Dickson, D. W., Sleiman, P. M. A., Wang, L.-S., Klei, L., Rademakers, R., de Silva, R., Litvan, I., et al. (2011) · Nature Genetics · doi:10.1038/ng.859 · Cited by 603 · see citing works
The Neuropathology of Chronic Traumatic Encephalopathy
McKee, A. C., Stein, T. D., Kiernan, P. T., & Alvarez, V. E. (2015) · Brain Pathology · doi:10.1111/bpa.12248 · Cited by 585 · see citing works
Self-citationClinical presentation of chronic traumatic encephalopathy
Stern, R. A., Daneshvar, D. H., Baugh, C. M., Seichepine, D. R., Montenigro, P. H., Riley, D. O., Fritts, N. G., Stamm, J. M., Robbins, C. A., McHale, L., et al. (2013) · Neurology · doi:10.1212/wnl.0b013e3182a55f7f · Cited by 564 · see citing works
Self-citationBaugh, C. M., Stamm, J. M., Riley, D. O., Gavett, B. E., Shenton, M. E., Lin, A., Nowinski, C. J., Cantu, R. C., McKee, A. C., & Stern, R. A. (2012) · Brain Imaging and Behavior · doi:10.1007/s11682-012-9164-5 · Cited by 486 · see citing works
Self-citationPerry, D. C., Sturm, V. E., Peterson, M. J., Pieper, C. F., Bullock, T., Boeve, B. F., Miller, B. L., Guskiewicz, K. M., Berger, M. S., Kramer, J. H., et al. (2016) · Journal of Neurosurgery · doi:10.3171/2015.2.jns14503 · Cited by 440 · see citing works
Military-related traumatic brain injury and neurodegeneration
McKee, A. C., & Robinson, M. E. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.04.003 · Cited by 423 · see citing works
Self-citationMcKee, A. C., Daneshvar, D. H., Alvarez, V. E., & Stein, T. D. (2014) · Acta Neuropathologica · doi:10.1007/s00401-013-1230-6 · Cited by 422 · see citing works
Self-citationThe clinical spectrum of sport-related traumatic brain injury
Jordan, B. D. (2013) · Nature Reviews Neurology · doi:10.1038/nrneurol.2013.33 · Cited by 347 · see citing works
Dementia Resulting From Traumatic Brain Injury: What Is the Pathology?
Shively, S., Scher, A. I., Perl, D. P., & Diaz-Arrastia, R. (2012) · Archives of Neurology · doi:10.1001/archneurol.2011.3747 · Cited by 346 · see citing works
Self-citationChronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank
Bieniek, K. F., Ross, O. A., Cormier, K. A., Walton, R. L., Soto-Ortolaza, A., Johnston, A. E., DeSaro, P., Boylan, K. B., Graff-Radford, N. R., Wszolek, Z. K., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1502-4 · Cited by 323 · see citing works
Self-citationHart, J., Kraut, M. A., Womack, K. B., Strain, J., Didehbani, N., Bartz, E., Conover, H., Mansinghani, S., Lu, H., & Cullum, C. M. (2013) · JAMA Neurology · doi:10.1001/2013.jamaneurol.340 · Cited by 315 · see citing works
Breedlove, E. L., Robinson, M., Talavage, T. M., Morigaki, K. E., Yoruk, U., O'Keefe, K., King, J., Leverenz, L. J., Gilger, J. W., & Nauman, E. A. (2012) · Journal of Biomechanics · doi:10.1016/j.jbiomech.2012.01.034 · Cited by 293 · see citing works
Hippocampal sclerosis in advanced age: clinical and pathological features
Nelson, P. T., Schmitt, F. A., Lin, Y., Abner, E. L., Jicha, G. A., Patel, E., Thomason, P. C., Neltner, J. H., Smith, C. D., Santacruz, K. S., et al. (2011) · Brain · doi:10.1093/brain/awr053 · Cited by 279 · see citing works
Molecular mechanisms of cognitive dysfunction following traumatic brain injury
Walker, K. R., & Tesco, G. (2013) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2013.00029 · Cited by 265 · see citing works
McKee, A. C., Stein, T. D., Huber, B. R., Crary, J. F., Bieniek, K., Dickson, D., Alvarez, V. E., Cherry, J. D., Farrell, K., Butler, M., et al. (2023) · Acta Neuropathologica · doi:10.1007/s00401-023-02540-w · Cited by 244 · see citing works
Self-citationMild traumatic brain injury: a risk factor for neurodegeneration
Gavett, B. E., Stern, R. A., Cantu, R. C., Nowinski, C. J., & McKee, A. C. (2010) · Alzheimer's Research & Therapy · doi:10.1186/alzrt42 · Cited by 216 · see citing works
Self-citationMaroon, J. C., Winkelman, R., Bost, J., Amos, A., Mathyssek, C., & Miele, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0117338 · Cited by 175 · see citing works
Chronic traumatic encephalopathy - confusion and controversies
Smith, D. H., Johnson, V. E., Trojanowski, J. Q., & Stewart, W. (2019) · Nature Reviews Neurology · doi:10.1038/s41582-018-0114-8 · Cited by 166 · see citing works
“New Old Pathologies”: AD, PART, and Cerebral Age-Related TDP-43 With Sclerosis (CARTS)
Nelson, P. T., Trojanowski, J. Q., Abner, E. L., Al-Janabi, O. M., Jicha, G. A., Schmitt, F. A., Smith, C. D., Fardo, D. W., Wang, W.-X., Kryscio, R. J., et al. (2016) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlw033 · Cited by 158 · see citing works
Hazrati, L.-N., Tartaglia, M. C., Diamandis, P., Davis, K. D., Green, R. E., Wennberg, R., Wong, J. C., Ezerins, L., & Tator, C. H. (2013) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2013.00222 · Cited by 146 · see citing works
Chronic traumatic encephalopathy: Where are we and where are we going?
Mez, J., Stern, R. A., & McKee, A. C. (2013) · Current Neurology and Neuroscience Reports · doi:10.1007/s11910-013-0407-7 · Cited by 120 · see citing works
Self-citationAssociation between concussion and mental health in former collegiate athletes
Kerr, Z. Y., Evenson, K. R., Rosamond, W. D., Mihalik, J. P., Guskiewicz, K. M., & Marshall, S. W. (2014) · Injury Epidemiology · doi:10.1186/s40621-014-0028-x · Cited by 107 · see citing works
A critical review of chronic traumatic encephalopathy
Iverson, G. L., Gardner, A. J., McCrory, P., Zafonte, R., & Castellani, R. J. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.008 · Cited by 103 · see citing works
Clinical appraisal of chronic traumatic encephalopathy: current perspectives and future directions
Gavett, B. E., Cantu, R. C., Shenton, M., Lin, A. P., Nowinski, C. J., McKee, A. C., & Stern, R. A. (2011) · Current Opinion in Neurology · doi:10.1097/wco.0b013e32834cd477 · Cited by 101 · see citing works
Current understanding of chronic traumatic encephalopathy
Baugh, C. M., Robbins, C. A., Stern, R. A., & McKee, A. C. (2014) · Current Treatment Options in Neurology · doi:10.1007/s11940-014-0306-5 · Cited by 94 · see citing works
Tau and TDP-43 proteinopathies: kindred pathologic cascades and genetic pleiotropy
Chornenkyy, Y., Fardo, D. W., & Nelson, P. T. (2019) · Laboratory Investigation · doi:10.1038/s41374-019-0196-y · Cited by 93 · see citing works
Traumatic encephalopathy: Review and provisional research diagnostic criteria
Victoroff, J. (2013) · Neurorehabilitation · doi:10.3233/nre-130839 · Cited by 91 · see citing works
Traumatic Brain Injury in the Elderly: Is it as Bad as we Think?
Mak, C. H. K., Wong, S. K. H., Wong, G. K., Ng, S., Wang, K. K. W., Lam, P. K., & Poon, W. S. (2012) · Current Translational Geriatrics and Experimental Gerontology Reports · doi:10.1007/s13670-012-0017-2 · Cited by 91 · see citing works
Chronic traumatic encephalopathy and risk of suicide in former athletes
Iverson, G. L. (2014) · British Journal of Sports Medicine · doi:10.1136/bjsports-2013-092935 · Cited by 90 · see citing works
Johnson, V. E., Stewart, W., Trojanowski, J. Q., & Smith, D. H. (2011) · Acta Neuropathologica · doi:10.1007/s00401-011-0909-9 · Cited by 87 · see citing works
LoBue, C., Munro, C., Schaffert, J., Didehbani, N., Hart, Batjer, H., & Cullum, C. M. (2019) · Journal of Alzheimer's Disease · doi:10.3233/jad-190028 · Cited by 86 · see citing works
The Need to Separate Chronic Traumatic Encephalopathy Neuropathology from Clinical Features
Iverson, G. L., Keene, C. D., Perry, G., & Castellani, R. J. (2017) · Journal of Alzheimer's Disease · doi:10.3233/jad-170654 · Cited by 72 · see citing works
“Gao and colleagues recently described a case of a man with ALS and no known history of neurotrauma who had CTE-like pathology in both depths of sulci and perivascular regions [34].”
InfluentialBlast TBI models, neuropathology, and implications for seizure risk.
Kovacs, S. K., Leonessa, F., & Ling, G. S. F. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00047 · Cited by 71 · see citing works
Pituitary pathology in traumatic brain injury: A review
Sav, A., Rotondo, F., Syro, L. V., Serna, C. A., & Kovacs, K. (2019) · Pituitary · doi:10.1007/s11102-019-00958-8 · Cited by 69 · see citing works
Josephs, K. A., Mackenzie, I., Frosch, M. P., Bigio, E. H., Neumann, M., Arai, T., Dugger, B. N., Ghetti, B., Grossman, M., Hasegawa, M., et al. (2019) · Brain · doi:10.1093/brain/awz224 · Cited by 66 · see citing works
Iverson, G. L., Luoto, T. M., Karhunen, P. J., & Castellani, R. J. (2019) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/nlz045 · Cited by 63 · see citing works
A New Hypothesis for Alzheimer’s Disease: The Lipid Invasion Model
Rudge, J. D. (2022) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-210299 · Cited by 58 · see citing works
DNA repair deficiency and senescence in concussed professional athletes involved in contact sports
Schwab, N., Grenier, K., & Hazrati, L.-N. (2019) · Acta Neuropathologica Communications · doi:10.1186/s40478-019-0822-3 · Cited by 47 · see citing works
Davis, G. A., Castellani, R. J., & McCrory, P. (2015) · Neurosurgery · doi:10.1227/neu.0000000000000722 · Cited by 47 · see citing works
Severe head injury and amyotrophic lateral sclerosis
Peters, T. L., Fang, F., Weibull, C. E., Sandler, D. P., Kamel, F., & Ye, W. (2013) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.3109/21678421.2012.754043 · Cited by 45 · see citing works
Head injury does not alter disease progression or neuropathologic outcomes in ALS
Fournier, C. N., Gearing, M., Upadhyayula, S. R., Klein, M., & Glass, J. D. (2015) · Neurology · doi:10.1212/wnl.0000000000001522 · Cited by 44 · see citing works
Head Injury and Amyotrophic Lateral Sclerosis: A Meta-Analysis
Liu, G., Ou, S., Cui, H., Li, X., Yin, Z., Gu, D., & Wang, Z. (2021) · Neuroepidemiology · doi:10.1159/000510987 · Cited by 41 · see citing works
Concomitant progressive supranuclear palsy and chronic traumatic encephalopathy in a boxer
Ling, H., Kara, E., Revesz, T., Lees, A. J., Plant, G. T., Martino, D., Houlden, H., Hardy, J., & Holton, J. L. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-24 · Cited by 27 · see citing works
Impact of traumatic brain injury on amyotrophic lateral sclerosis: from bedside to bench
Franz, C. K., Joshi, D., Daley, E. L., Grant, R. A., Dalamagkas, K., Leung, A., Finan, J. D., & Kiskinis, E. (2019) · Journal of Neurophysiology · doi:10.1152/jn.00572.2018 · Cited by 26 · see citing works
- Authors
- McKee, A. C., Gavett, B. E., Stern, R. A., Nowinski, C. J., Cantu, R. C., Kowall, N. W., Perl, D. P., Hedley-Whyte, E. T., Price, B., Sullivan, C., Morin, P., Lee, H.-S., Kubilus, C. A., Daneshvar, D. H., Wulff, M., & Budson, A. E.
- Affiliations
- Boston University (US)
- Corresponding author
- McKee, Ann C.
- ORCID
- Venue
- Journal of Neuropathology & Experimental Neurology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-09
- Volume
- 69
- Issue
- 9
- Pages
- 918-929
- ISSN
- 0022-3069 (ISSN-L)
- 1554-6578
- PMC
- PMC2951281
- OpenAlex
- W2077024919
- Cited by
- 659
- References
- 75
- Citations by year
- 2026: 13 · 2025: 25 · 2024: 26 · 2023: 30 · 2022: 36 · 2021: 43 · 2020: 27 · 2019: 50 · 2018: 36 · 2017: 44 · 2016: 44 · 2015: 67 · 2014: 48 · 2013: 73 · 2012: 47
- FWCI
- 32.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuropathology & Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- U.S. Department of Veterans Affairs (AG13846, P30 AG13846, CSP501)
- National Operating Committee on Standards for Athletic Equipment
- National Institute on Aging (P50 AG 05138, AG 13846, P01 AG 02219, P50AG005138, 0572063345–5, 0572063345, P50 AG05134, supplement 0572063345, P30AG013846, P50AG005134, P01AG002219, P30-AG13846))
- Topics
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Epidemiology › Traumatic Brain Injury Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- chronic traumatic encephalopathy, TDP-43 proteinopathy, motor neuron disease, repetitive head injury, tauopathy, neurofibrillary tangles, frontotemporal lobar degeneration, corticospinal tract degeneration, collision sports, athletes, amyotrophic lateral sclerosis
- MeSH terms
- Adult, Aged, Aged, 80 and over, Athletic Injuries, Brain, DNA-Binding Proteins, Humans, Middle Aged, Motor Neuron Disease, Brain Injury, Chronic, Athletes, TDP-43 Proteinopathies
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