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Semin Neurol 2020; 40(04): 384-393
DOI: 10.1055/s-0040-1713628
Review Article

Chronic Traumatic Encephalopathy and Neuropathological Comorbidities

Thor D. Stein 
1   Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts
2   Boston University Alzheimer's Disease and CTE Center, Boston University School of Medicine, Boston, Massachusetts
3   Departments of Research and Pathology & Laboratory Medicine, VA Boston Healthcare System, Boston, Massachusetts
4   Department of Veterans Affairs Medical Center, Bedford, Massachusetts
,
John F. Crary
5   Department of Pathology, Neuropathology Brain Bank & Research Core, Ronald M. Loeb Center for Alzheimer's Disease, Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York
› Author Affiliations Funding This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Clinical Sciences Research and Development Merit Award (I01-CX001038); Veterans Affairs Biorepository (BX002466); Department of Defense (W81XWH-14–1-0399); National Institute of Aging (RF1AG054156, R56AG057768, R01AG057768, R01AG054008, R01NS095252, R01AG062348, RF1AG060961); National Institute of Neurological Disorders and Stroke (U01NS086659); National Institute of Aging Boston University AD Center (P30AG13846; supplement 0572063345–5); Concussion Legacy Foundation, the Tau Consortium (Rainwater Charitable Trust), and the Alzheimer's Association (NIRG-15–363188). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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Abstract

With age, the presence of multiple neuropathologies in a single individual becomes increasingly common. Given that traumatic brain injury and the repetitive head impacts (RHIs) that occur in contact sports have been associated with the development of many neurodegenerative diseases, including chronic traumatic encephalopathy (CTE), Alzheimer's disease, Lewy body disease, and amyotrophic lateral sclerosis, it is becoming critical to understand the relationship and interactions between these pathologies. In fact, comorbid pathology is common in CTE and likely influenced by both age and the severity and type of exposure to RHI as well as underlying genetic predisposition. Here, we review the major comorbid pathologies seen with CTE and in former contact sports athletes and discuss what is known about the associations between RHI, age, and the development of neuropathologies. In addition, we examine the distinction between CTE and age-related pathology including primary age-related tauopathy and age-related tau astrogliopathy.

Keywords

chronic traumatic encephalopathy - traumatic brain injury - neurodegenerative disease - Alzheimer's disease - comorbidity


Publication History

Article published online:
30 June 2020

© 2020. Thieme. All rights reserved.

Thieme Medical Publishers
333 Seventh Avenue, New York, NY 10001, USA.

 

  • References

  • 1 Boyle PA, Yu L, Wilson RS, Leurgans SE, Schneider JA, Bennett DA. Person-specific contribution of neuropathologies to cognitive loss in old age. Ann Neurol 2018; 83 (01) 74-83
    CrossrefPubMedGoogle Scholar
  • 2 Robinson JL, Lee EB, Xie SX. , et al. Neurodegenerative disease concomitant proteinopathies are prevalent, age-related and APOE4-associated. Brain 2018; 141 (07) 2181-2193
    CrossrefPubMedGoogle Scholar
  • 3 Barnes DE, Byers AL, Gardner RC, Seal KH, Boscardin WJ, Yaffe K. Association of mild traumatic brain injury with and without loss of consciousness with dementia in US Military Veterans. JAMA Neurol 2018; 75 (09) 1055-1061
    CrossrefPubMedGoogle Scholar
  • 4 Plassman BL, Havlik RJ, Steffens DC. , et al. Documented head injury in early adulthood and risk of Alzheimer's disease and other dementias. Neurology 2000; 55 (08) 1158-1166
    CrossrefPubMedGoogle Scholar
  • 5 Crane PK, Gibbons LE, Dams-O'Connor K. , et al. Association of traumatic brain injury with late-life neurodegenerative conditions and neuropathologic findings. JAMA Neurol 2016; 73 (09) 1062-1069
    CrossrefPubMedGoogle Scholar
  • 6 Gardner RC, Byers AL, Barnes DE, Li Y, Boscardin J, Yaffe K. Mild TBI and risk of Parkinson disease. Neurology 2018; 90 (20) e1771-e1779
    CrossrefPubMedGoogle Scholar
  • 7 Sugarman MA, McKee AC, Stein TD. , et al. Failure to detect an association between self-reported traumatic brain injury and Alzheimer's disease neuropathology and dementia. Alzheimers Dement 2019; 15 (05) 686-698
    CrossrefPubMedGoogle Scholar
  • 8 Dams-O'Connor K, Guetta G, Hahn-Ketter AE, Fedor A. Traumatic brain injury as a risk factor for Alzheimer's disease: current knowledge and future directions. Neurodegener Dis Manag 2016; 6 (05) 417-429
    CrossrefPubMedGoogle Scholar
  • 9 Plassman BL, Grafman J. Traumatic brain injury and late-life dementia. Handb Clin Neurol 2015; 128: 711-722
    CrossrefPubMedGoogle Scholar
  • 10 Pischiutta F, Micotti E, Hay JR. , et al. Single severe traumatic brain injury produces progressive pathology with ongoing contralateral white matter damage one year after injury. Exp Neurol 2018; 300: 167-178
    CrossrefPubMedGoogle Scholar
  • 11 Ikonomovic MD, Uryu K, Abrahamson EE. , et al. Alzheimer's pathology in human temporal cortex surgically excised after severe brain injury. Exp Neurol 2004; 190 (01) 192-203
    CrossrefPubMedGoogle Scholar
  • 12 Smith DH, Chen X-H, Iwata A, Graham DI. Amyloid beta accumulation in axons after traumatic brain injury in humans. J Neurosurg 2003; 98 (05) 1072-1077
    CrossrefPubMedGoogle Scholar
  • 13 McKee AC, Cairns NJ, Dickson DW. , et al; TBI/CTE group. The first NINDS/NIBIB consensus meeting to define neuropathological criteria for the diagnosis of chronic traumatic encephalopathy. Acta Neuropathol 2016; 131 (01) 75-86
    CrossrefPubMedGoogle Scholar
  • 14 Zetterberg H, Blennow K. Chronic traumatic encephalopathy: fluid biomarkers. Handb Clin Neurol 2018; 158: 323-333
    CrossrefPubMedGoogle Scholar
  • 15 Lin A, Charney M, Shenton ME, Koerte IK. Chronic traumatic encephalopathy: neuroimaging biomarkers. Handb Clin Neurol 2018; 158: 309-322
    CrossrefPubMedGoogle Scholar
  • 16 Roberts GW, Gentleman SM, Lynch A, Murray L, Landon M, Graham DI. Beta amyloid protein deposition in the brain after severe head injury: implications for the pathogenesis of Alzheimer's disease. J Neurol Neurosurg Psychiatry 1994; 57 (04) 419-425
    CrossrefPubMedGoogle Scholar
  • 17 Roberts GW, Gentleman SM, Lynch A, Graham DI. beta A4 amyloid protein deposition in brain after head trauma. Lancet 1991; 338 (8780): 1422-1423
    CrossrefPubMedGoogle Scholar
  • 18 Gentleman SM, Greenberg BD, Savage MJ. , et al. A beta 42 is the predominant form of amyloid beta-protein in the brains of short-term survivors of head injury. Neuroreport 1997; 8 (06) 1519-1522
    CrossrefPubMedGoogle Scholar
  • 19 Olsson A, Csajbok L, Ost M. , et al. Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. J Neurol 2004; 251 (07) 870-876
    CrossrefPubMedGoogle Scholar
  • 20 Roberts GW, Allsop D, Bruton C. The occult aftermath of boxing. J Neurol Neurosurg Psychiatry 1990; 53 (05) 373-378
    CrossrefPubMedGoogle Scholar
  • 21 Tokuda T, Ikeda S, Yanagisawa N, Ihara Y, Glenner GG. Re-examination of ex-boxers' brains using immunohistochemistry with antibodies to amyloid beta-protein and tau protein. Acta Neuropathol 1991; 82 (04) 280-285
    CrossrefPubMedGoogle Scholar
  • 22 Hof PR, Bouras C, Buée L, Delacourte A, Perl DP, Morrison JH. Differential distribution of neurofibrillary tangles in the cerebral cortex of dementia pugilistica and Alzheimer's disease cases. Acta Neuropathol 1992; 85 (01) 23-30
    CrossrefPubMedGoogle Scholar
  • 23 Geddes JF, Vowles GH, Robinson SF, Sutcliffe JC. Neurofibrillary tangles, but not Alzheimer-type pathology, in a young boxer. Neuropathol Appl Neurobiol 1996; 22 (01) 12-16
    CrossrefPubMedGoogle Scholar
  • 24 Omalu BI, DeKosky ST, Minster RL, Kamboh MI, Hamilton RL, Wecht CH. Chronic traumatic encephalopathy in a National Football League player. Neurosurgery 2005; 57 (01) 128-134 , discussion 128–134
    CrossrefPubMedGoogle Scholar
  • 25 McKee AC, Cantu RC, Nowinski CJ. , et al. Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol 2009; 68 (07) 709-735
    CrossrefPubMedGoogle Scholar
  • 26 Goldstein LE, Fisher AM, Tagge CA. , et al. Chronic traumatic encephalopathy in blast-exposed military veterans and a blast neurotrauma mouse model. Sci Transl Med 2012; 4 (134) 134ra60
    CrossrefPubMedGoogle Scholar
  • 27 McKee AC, Stern RA, Nowinski CJ. , et al. The spectrum of disease in chronic traumatic encephalopathy. Brain 2013; 136 (Pt 1): 43-64
    CrossrefPubMedGoogle Scholar
  • 28 Stein TD, Montenigro PH, Alvarez VE. , et al. Beta-amyloid deposition in chronic traumatic encephalopathy. Acta Neuropathol 2015; 130 (01) 21-34
    CrossrefPubMedGoogle Scholar
  • 29 Montine TJ, Phelps CH, Beach TG. , et al; National Institute on Aging; Alzheimer's Association. National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol 2012; 123 (01) 1-11
    CrossrefPubMedGoogle Scholar
  • 30 Braak H, Thal DR, Ghebremedhin E, Del Tredici K. Stages of the pathologic process in Alzheimer disease: age categories from 1 to 100 years. J Neuropathol Exp Neurol 2011; 70 (11) 960-969
    CrossrefPubMedGoogle Scholar
  • 31 Lee EB, Kinch K, Johnson VE, Trojanowski JQ, Smith DH, Stewart W. Chronic traumatic encephalopathy is a common co-morbidity, but less frequent primary dementia in former soccer and rugby players. Acta Neuropathol 2019; 138 (03) 389-399
    CrossrefPubMedGoogle Scholar
  • 32 Keable A, Fenna K, Yuen HM. , et al. Deposition of amyloid β in the walls of human leptomeningeal arteries in relation to perivascular drainage pathways in cerebral amyloid angiopathy. Biochim Biophys Acta 2016; 1862 (05) 1037-1046
    CrossrefPubMedGoogle Scholar
  • 33 Charidimou A, Boulouis G, Roongpiboonsopit D. , et al. Cortical superficial siderosis multifocality in cerebral amyloid angiopathy: a prospective study. Neurology 2017; 89 (21) 2128-2135
    CrossrefPubMedGoogle Scholar
  • 34 Lauer A, van Veluw SJ, William CM. , et al. Microbleeds on MRI are associated with microinfarcts on autopsy in cerebral amyloid angiopathy. Neurology 2016; 87 (14) 1488-1492
    CrossrefPubMedGoogle Scholar
  • 35 Attems J, Jellinger KA, Lintner F. Alzheimer's disease pathology influences severity and topographical distribution of cerebral amyloid angiopathy. Acta Neuropathol 2005; 110 (03) 222-231
    CrossrefPubMedGoogle Scholar
  • 36 Pfeifer LA, White LR, Ross GW, Petrovitch H, Launer LJ. Cerebral amyloid angiopathy and cognitive function: the HAAS autopsy study. Neurology 2002; 58 (11) 1629-1634
    CrossrefPubMedGoogle Scholar
  • 37 Tian J, Shi J, Bailey K, Mann DMA. Negative association between amyloid plaques and cerebral amyloid angiopathy in Alzheimer's disease. Neurosci Lett 2003; 352 (02) 137-140
    CrossrefPubMedGoogle Scholar
  • 38 Vinters HV. Cerebral amyloid angiopathy. A critical review. Stroke 1987; 18 (02) 311-324
    CrossrefPubMedGoogle Scholar
  • 39 Tian J, Shi J, Bailey K, Mann DMA. Relationships between arteriosclerosis, cerebral amyloid angiopathy and myelin loss from cerebral cortical white matter in Alzheimer's disease. Neuropathol Appl Neurobiol 2004; 30 (01) 46-56
    CrossrefPubMedGoogle Scholar
  • 40 Attems J, Jellinger K, Thal DR, Van Nostrand W. Review: sporadic cerebral amyloid angiopathy. Neuropathol Appl Neurobiol 2011; 37 (01) 75-93
    CrossrefPubMedGoogle Scholar
  • 41 Itoh Y, Yamada M, Hayakawa M, Otomo E, Miyatake T. Cerebral amyloid angiopathy: a significant cause of cerebellar as well as lobar cerebral hemorrhage in the elderly. J Neurol Sci 1993; 116 (02) 135-141
    CrossrefPubMedGoogle Scholar
  • 42 Charidimou A, Gang Q, Werring DJ. Sporadic cerebral amyloid angiopathy revisited: recent insights into pathophysiology and clinical spectrum. J Neurol Neurosurg Psychiatry 2012; 83 (02) 124-137
    CrossrefPubMedGoogle Scholar
  • 43 Keage HAD, Carare RO, Friedland RP. , et al. Population studies of sporadic cerebral amyloid angiopathy and dementia: a systematic review. BMC Neurol 2009; 9 (01) 3
    CrossrefPubMedGoogle Scholar
  • 44 Leclercq PD, Murray LS, Smith C, Graham DI, Nicoll JA, Gentleman SM. Cerebral amyloid angiopathy in traumatic brain injury: association with apolipoprotein E genotype. J Neurol Neurosurg Psychiatry 2005; 76 (02) 229-233
    CrossrefPubMedGoogle Scholar
  • 45 Weissberg I, Veksler R, Kamintsky L. , et al. Imaging blood-brain barrier dysfunction in football players. JAMA Neurol 2014; 71 (11) 1453-1455
    CrossrefPubMedGoogle Scholar
  • 46 Standring OJ, Friedberg J, Tripodis Y. , et al. Contact sport participation and chronic traumatic encephalopathy are associated with altered severity and distribution of cerebral amyloid angiopathy. Acta Neuropathol 2019; 138 (03) 401-413
    CrossrefPubMedGoogle Scholar
  • 47 Broglio SP, Sosnoff JJ, Shin S, He X, Alcaraz C, Zimmerman J. Head impacts during high school football: a biomechanical assessment. J Athl Train 2009; 44 (04) 342-349
    CrossrefPubMedGoogle Scholar
  • 48 Crisco JJ, Fiore R, Beckwith JG. , et al. Frequency and location of head impact exposures in individual collegiate football players. J Athl Train 2010; 45 (06) 549-559
    CrossrefPubMedGoogle Scholar
  • 49 Ghajari M, Hellyer PJ, Sharp DJ. Computational modelling of traumatic brain injury predicts the location of chronic traumatic encephalopathy pathology. Brain 2017; 140 (02) 333-343
    CrossrefPubMedGoogle Scholar
  • 50 Parkinson J. An essay on the shaking palsy. 1817. J Neuropsychiatry Clin Neurosci 2002; 14 (02) 223-236 , discussion 222
    CrossrefPubMedGoogle Scholar
  • 51 Gardner RC, Burke JF, Nettiksimmons J, Goldman S, Tanner CM, Yaffe K. Traumatic brain injury in later life increases risk for Parkinson disease. Ann Neurol 2015; 77 (06) 987-995
    CrossrefPubMedGoogle Scholar
  • 52 Perry DC, Sturm VE, Peterson MJ. , et al. Association of traumatic brain injury with subsequent neurological and psychiatric disease: a meta-analysis. J Neurosurg 2016; 124 (02) 511-526
    CrossrefPubMedGoogle Scholar
  • 53 Lee P-C, Bordelon Y, Bronstein J, Ritz B. Traumatic brain injury, paraquat exposure, and their relationship to Parkinson disease. Neurology 2012; 79 (20) 2061-2066
    CrossrefPubMedGoogle Scholar
  • 54 Jafari S, Etminan M, Aminzadeh F, Samii A. Head injury and risk of Parkinson disease: a systematic review and meta-analysis. Mov Disord 2013; 28 (09) 1222-1229
    CrossrefPubMedGoogle Scholar
  • 55 Stern RA, Daneshvar DH, Baugh CM. , et al. Clinical presentation of chronic traumatic encephalopathy. Neurology 2013; 81 (13) 1122-1129
    CrossrefPubMedGoogle Scholar
  • 56 Montenigro PH, Corp DT, Stein TD, Cantu RC, Stern RA. Chronic traumatic encephalopathy: historical origins and current perspective. Annu Rev Clin Psychol 2015; 11 (January): 309-330
    CrossrefPubMedGoogle Scholar
  • 57 Tarazi A, Tator CH, Wennberg R. , et al. Motor function in former professional football players with history of multiple concussions. J Neurotrauma 2018; 35 (08) 1003-1007
    CrossrefPubMedGoogle Scholar
  • 58 Adams JW, Alvarez VE, Mez J. , et al. Lewy body pathology and chronic traumatic encephalopathy associated with contact sports. J Neuropathol Exp Neurol 2018; 77 (09) 757-768
    CrossrefPubMedGoogle Scholar
  • 59 Weisskopf MG, Cudkowicz ME, Johnson N. Military service and amyotrophic lateral sclerosis in a population-based cohort. Epidemiology 2015; 26 (06) 831-838
    CrossrefPubMedGoogle Scholar
  • 60 Cragg JJ, Johnson NJ, Weisskopf MG. Military service and amyotrophic lateral sclerosis in a population-based cohort: extended follow-up 1979-2011. Epidemiology 2017; 28 (02) e15-e16
    CrossrefPubMedGoogle Scholar
  • 61 Lehman EJ, Hein MJ, Baron SL, Gersic CM. Neurodegenerative causes of death among retired National Football League players. Neurology 2012; 79 (19) 1970-1974
    CrossrefPubMedGoogle Scholar
  • 62 Brady CB, Trevor KT, Stein TD. , et al. The Department of Veterans Affairs Biorepository Brain Bank: a national resource for amyotrophic lateral sclerosis research. Amyotroph Lateral Scler Frontotemporal Degener 2013; 14 (7-8): 591-597
    CrossrefPubMedGoogle Scholar
  • 63 Mez J, Daneshvar DH, Kiernan PT. , et al. Clinicopathological evaluation of chronic traumatic encephalopathy in players of American football. JAMA 2017; 318 (04) 360-370
    CrossrefPubMedGoogle Scholar
  • 64 Chen H, Richard M, Sandler DP, Umbach DM, Kamel F. Head injury and amyotrophic lateral sclerosis. Am J Epidemiol 2007; 166 (07) 810-816
    CrossrefPubMedGoogle Scholar
  • 65 Fournier CN, Gearing M, Upadhyayula SR, Klein M, Glass JD. Head injury does not alter disease progression or neuropathologic outcomes in ALS. Neurology 2015; 84 (17) 1788-1795
    CrossrefPubMedGoogle Scholar
  • 66 Schmidt S, Kwee LC, Allen KD, Oddone EZ. Association of ALS with head injury, cigarette smoking and APOE genotypes. J Neurol Sci 2010; 291 (1-2): 22-29
    CrossrefPubMedGoogle Scholar
  • 67 Walt GS, Burris HM, Brady CB. , et al. Chronic traumatic encephalopathy within an amyotrophic lateral sclerosis brain bank cohort. J Neuropathol Exp Neurol 2018; 77 (12) 1091-1100
    CrossrefPubMedGoogle Scholar
  • 68 Keene CD, Latimer CS, Steele LM, Mac Donald CL. First confirmed case of chronic traumatic encephalopathy in a professional bull rider. Acta Neuropathol 2018; 135 (02) 303-305
    CrossrefPubMedGoogle Scholar
  • 69 Brettschneider J, Del Tredici K, Toledo JB. , et al. Stages of pTDP-43 pathology in amyotrophic lateral sclerosis. Ann Neurol 2013; 74 (01) 20-38
    CrossrefPubMedGoogle Scholar
  • 70 Alosco ML, Duskin J, Besser LM. , et al. Modeling the relationships among late-life body mass index, cerebrovascular disease, and Alzheimer's disease neuropathology in an autopsy sample of 1,421 subjects from the National Alzheimer's Coordinating Center data set. J Alzheimers Dis 2017; 57 (03) 953-968
    CrossrefPubMedGoogle Scholar
  • 71 Deramecourt V, Slade JY, Oakley AE. , et al. Staging and natural history of cerebrovascular pathology in dementia. Neurology 2012; 78 (14) 1043-1050
    CrossrefPubMedGoogle Scholar
  • 72 Kalaria RN, Ballard C. Overlap between pathology of Alzheimer disease and vascular dementia. Alzheimer Dis Assoc Disord 1999; 13 (Suppl. 03) S115-S123
    CrossrefPubMedGoogle Scholar
  • 73 Nelson AR, Sweeney MD, Sagare AP, Zlokovic BV. Neurovascular dysfunction and neurodegeneration in dementia and Alzheimer's disease. Biochim Biophys Acta 2016; 1862 (05) 887-900
    CrossrefPubMedGoogle Scholar
  • 74 Toledo JB, Arnold SE, Raible K. , et al. Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer's Coordinating Centre. Brain 2013; 136 (Pt 9): 2697-2706
    CrossrefPubMedGoogle Scholar
  • 75 Arvanitakis Z, Capuano AW, Leurgans SE, Bennett DA, Schneider JA. Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol 2016; 15 (09) 934-943
    CrossrefPubMedGoogle Scholar
  • 76 Baron SL, Hein MJ, Lehman E, Gersic CM. Body mass index, playing position, race, and the cardiovascular mortality of retired professional football players. Am J Cardiol 2012; 109 (06) 889-896
    CrossrefPubMedGoogle Scholar
  • 77 Tucker AM, Vogel RA, Lincoln AE. , et al. Prevalence of cardiovascular disease risk factors among National Football League players. JAMA 2009; 301 (20) 2111-2119
    CrossrefPubMedGoogle Scholar
  • 78 Corsellis JA, Bruton CJ, Freeman-Browne D. The aftermath of boxing. Psychol Med 1973; 3 (03) 270-303
    CrossrefPubMedGoogle Scholar
  • 79 Buée L, Hof PR, Bouras C. , et al. Pathological alterations of the cerebral microvasculature in Alzheimer's disease and related dementing disorders. Acta Neuropathol 1994; 87 (05) 469-480
    CrossrefPubMedGoogle Scholar
  • 80 Doherty CP, O'Keefe E, Wallace E. , et al. Blood-brain barrier dysfunction as a hallmark pathology in chronic traumatic encephalopathy. J Neuropathol Exp Neurol 2016; 75 (07) 656-662
    CrossrefPubMedGoogle Scholar
  • 81 Alosco ML, Stein TD, Tripodis Y. , et al. Association of white matter rarefaction, arteriolosclerosis, and tau with dementia in chronic traumatic encephalopathy. JAMA Neurol 2019 (August) Doi: 10.1001/jamaneurol.2019.2244
    PubMedGoogle Scholar
  • 82 Kovacs GG. Invited review: neuropathology of tauopathies: principles and practice. Neuropathol Appl Neurobiol 2015; 41 (01) 3-23
    CrossrefPubMedGoogle Scholar
  • 83 Spillantini MG, Goedert M, Crowther RA, Murrell JR, Farlow MR, Ghetti B. Familial multiple system tauopathy with presenile dementia: a disease with abundant neuronal and glial tau filaments. Proc Natl Acad Sci U S A 1997; 94 (08) 4113-4118
    CrossrefPubMedGoogle Scholar
  • 84 Bouras C, Hof PR, Morrison JH. Neurofibrillary tangle densities in the hippocampal formation in a non-demented population define subgroups of patients with differential early pathologic changes. Neurosci Lett 1993; 153 (02) 131-135
    CrossrefPubMedGoogle Scholar
  • 85 Braak H, Del Tredici K. Evolutional aspects of Alzheimer's disease pathogenesis. J Alzheimers Dis 2013; 33 (Suppl. 01) S155-S161
    PubMedGoogle Scholar
  • 86 Crary JF, Trojanowski JQ, Schneider JA. , et al. Primary age-related tauopathy (PART): a common pathology associated with human aging. Acta Neuropathol 2014; 128 (06) 755-766
    CrossrefPubMedGoogle Scholar
  • 87 Takao M, Hirose N, Arai Y, Mihara B, Mimura M. Neuropathology of supercentenarians - four autopsy case studies. Acta Neuropathol Commun 2016; 4 (01) 97
    CrossrefPubMedGoogle Scholar
  • 88 Besser LM, Crary JF, Mock C, Kukull WA. Comparison of symptomatic and asymptomatic persons with primary age-related tauopathy. Neurology 2017; 89 (16) 1707-1715
    CrossrefPubMedGoogle Scholar
  • 89 Abner EL, Kryscio RJ, Schmitt FA. , et al. Outcomes after diagnosis of mild cognitive impairment in a large autopsy series. Ann Neurol 2017; 81 (04) 549-559
    CrossrefPubMedGoogle Scholar
  • 90 Cerami C, Dodich A, Iannaccone S. , et al. A biomarker study in long-lasting amnestic mild cognitive impairment. Alzheimers Res Ther 2018; 10 (01) 42
    CrossrefPubMedGoogle Scholar
  • 91 Bell WR, An Y, Kageyama Y. , et al. Neuropathologic, genetic, and longitudinal cognitive profiles in primary age-related tauopathy (PART) and Alzheimer's disease. Alzheimers Dement 2019; 15 (01) 8-16
    CrossrefPubMedGoogle Scholar
  • 92 Besser LM, Mock C, Teylan MA, Hassenstab J, Kukull WA, Crary JF. Differences in cognitive impairment in primary age-related tauopathy versus Alzheimer disease. J Neuropathol Exp Neurol 2019; 78 (03) 219-228
    CrossrefPubMedGoogle Scholar
  • 93 Jefferson-George KS, Wolk DA, Lee EB, McMillan CT. Cognitive decline associated with pathological burden in primary age-related tauopathy. Alzheimers Dement 2017; 13 (09) 1048-1053
    CrossrefPubMedGoogle Scholar
  • 94 McMillan CT, Lee EB, Jefferson-George K. , et al. Alzheimer's genetic risk is reduced in primary age-related tauopathy: a potential model of resistance?. Ann Clin Transl Neurol 2018; 5 (08) 927-934
    CrossrefPubMedGoogle Scholar
  • 95 Santa-Maria I, Haggiagi A, Liu X. , et al. The MAPT H1 haplotype is associated with tangle-predominant dementia. Acta Neuropathol 2012; 124 (05) 693-704
    CrossrefPubMedGoogle Scholar
  • 96 Janocko NJ, Brodersen KA, Soto-Ortolaza AI. , et al. Neuropathologically defined subtypes of Alzheimer's disease differ significantly from neurofibrillary tangle-predominant dementia. Acta Neuropathol 2012; 124 (05) 681-692
    CrossrefPubMedGoogle Scholar
  • 97 Kovacs GG, Ferrer I, Grinberg LT. , et al. Aging-related tau astrogliopathy (ARTAG): harmonized evaluation strategy. Acta Neuropathol 2016; 131 (01) 87-102
    CrossrefPubMedGoogle Scholar
  • 98 Forrest SL, Kril JJ, Wagner S. , et al. Chronic traumatic encephalopathy (CTE) is absent from a European community-based aging cohort while cortical aging-related tau astrogliopathy (ARTAG) is highly prevalent. J Neuropathol Exp Neurol 2019; 78 (05) 398-405
    CrossrefPubMedGoogle Scholar
  • 99 Yamada T, McGeer PL, McGeer EG. Appearance of paired nucleated, Tau-positive glia in patients with progressive supranuclear palsy brain tissue. Neurosci Lett 1992; 135 (01) 99-102
    CrossrefPubMedGoogle Scholar
  • 100 Feany MB, Dickson DW. Widespread cytoskeletal pathology characterizes corticobasal degeneration. Am J Pathol 1995; 146 (06) 1388-1396
    PubMedGoogle Scholar
  • 101 Kovacs GG, Xie SX, Robinson JL. , et al. Sequential stages and distribution patterns of aging-related tau astrogliopathy (ARTAG) in the human brain. Acta Neuropathol Commun 2018; 6 (01) 50
    CrossrefPubMedGoogle Scholar
  • 102 Kovacs GG, Robinson JL, Xie SX. , et al. Evaluating the patterns of aging-related tau astrogliopathy unravels novel insights into brain aging and neurodegenerative diseases. J Neuropathol Exp Neurol 2017; 76 (04) 270-288
    CrossrefPubMedGoogle Scholar
  • 103 Munoz DG, Ros R, Fatas M, Bermejo F, de Yebenes JG. Progressive nonfluent aphasia associated with a new mutation V363I in tau gene. Am J Alzheimers Dis Other Demen 2007; 22 (04) 294-299
    CrossrefPubMedGoogle Scholar
  • 104 Mesulam M, Wicklund A, Johnson N. , et al. Alzheimer and frontotemporal pathology in subsets of primary progressive aphasia. Ann Neurol 2008; 63 (06) 709-719
    CrossrefPubMedGoogle Scholar
  • 105 Bigio EH, Mishra M, Hatanpaa KJ. , et al. TDP-43 pathology in primary progressive aphasia and frontotemporal dementia with pathologic Alzheimer disease. Acta Neuropathol 2010; 120 (01) 43-54
    CrossrefPubMedGoogle Scholar
  • 106 Robinson JL, Corrada MM, Kovacs GG. , et al. Non-Alzheimer's contributions to dementia and cognitive resilience in The 90+ Study. Acta Neuropathol 2018; 136 (03) 377-388
    CrossrefPubMedGoogle Scholar
  • 107 Morgello S, Jacobs M, Murray J. , et al. Alzheimer's disease neuropathology may not predict functional impairment in HIV: a report of two individuals. J Neurovirol 2018; 24 (05) 629-637
    CrossrefPubMedGoogle Scholar
  • 108 Gómez-Tortosa E, Baradaran-Heravi Y, González Alvarez V. , et al; EU EOD Consortium. Presence of tau astrogliopathy in frontotemporal dementia caused by a novel Grn nonsense (Trp2*) mutation. Neurobiol Aging 2019; 76: 214.e11-214.e15
    CrossrefPubMedGoogle Scholar
  • 109 Baskota SU, Lopez OL, Greenamyre JT, Kofler J. Spectrum of tau pathologies in Huntington's disease. Lab Invest 2019; 99 (07) 1068-1077
    CrossrefPubMedGoogle Scholar
  • 110 Hsu ET, Gangolli M, Su S. , et al. Astrocytic degeneration in chronic traumatic encephalopathy. Acta Neuropathol 2018; 136 (06) 955-972
    CrossrefPubMedGoogle Scholar
  • 111 Braak H, Braak E. Argyrophilic grains: characteristic pathology of cerebral cortex in cases of adult onset dementia without Alzheimer changes. Neurosci Lett 1987; 76 (01) 124-127
    CrossrefPubMedGoogle Scholar
  • 112 Josephs KA, Whitwell JL, Parisi JE. , et al. Argyrophilic grains: a distinct disease or an additive pathology?. Neurobiol Aging 2008; 29 (04) 566-573
    CrossrefPubMedGoogle Scholar
  • 113 Rodriguez RD, Grinberg LT. Argyrophilic grain disease: an underestimated tauopathy. Dement Neuropsychol 2015; 9 (01) 2-8
    CrossrefPubMedGoogle Scholar
  • 114 McKee AC, Stein TD, Kiernan PT, Alvarez VE. The neuropathology of chronic traumatic encephalopathy. Brain Pathol 2015; 25 (03) 350-364
    CrossrefPubMedGoogle Scholar
  • 115 Armstrong RA, McKee AC, Stein TD, Alvarez VE, Cairns NJ. A quantitative study of tau pathology in 11 cases of chronic traumatic encephalopathy. Neuropathol Appl Neurobiol 2017; 43 (02) 154-166
    CrossrefPubMedGoogle Scholar
  • 116 Ling H, Kara E, Revesz T. , et al. Concomitant progressive supranuclear palsy and chronic traumatic encephalopathy in a boxer. Acta Neuropathol Commun 2014; 2 (01) 24
    CrossrefPubMedGoogle Scholar
  • 117 Golbe LI, Rubin RS, Cody RP. , et al. Follow-up study of risk factors in progressive supranuclear palsy. Neurology 1996; 47 (01) 148-154
    CrossrefPubMedGoogle Scholar
  • 118 Nemani SK, Notari S, Cali I. , et al. Co-occurrence of chronic traumatic encephalopathy and prion disease. Acta Neuropathol Commun 2018; 6 (01) 140
    CrossrefPubMedGoogle Scholar
  • 119 Koga S, Dickson DW, Bieniek KF. Chronic traumatic encephalopathy pathology in multiple system atrophy. J Neuropathol Exp Neurol 2016; 75 (10) 963-970
    CrossrefPubMedGoogle Scholar
  • 120 Farrell M, Aherne S, O'Riordan S, O'Keeffe E, Greene C, Campbell M. Blood-brain barrier dysfunction in a boxer with chronic traumatic encephalopathy and schizophrenia. Clin Neuropathol 2019; 38 (02) 51-58
    CrossrefPubMedGoogle Scholar
  • 121 Molloy C, Conroy RM, Cotter DR, Cannon M. Is traumatic brain injury a risk factor for schizophrenia? A meta-analysis of case-controlled population-based studies. Schizophr Bull 2011; 37 (06) 1104-1110
    CrossrefPubMedGoogle Scholar
  • 122 Stein TD, Alvarez VE, McKee AC. Concussion in chronic traumatic encephalopathy. Curr Pain Headache Rep 2015; 19 (10) 47
    CrossrefPubMedGoogle Scholar