Barrio, J R; Small, G W; Wong, K P; Huang, S C; Liu, J; Merrill, D A; Giza, C C; Fitzsimmons, R P; Omalu, B; Bailes, J; Kepe, V
In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344] Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 16, pp. E2039–47, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged
@article{Barrio2015,
title = {In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344]},
author = {Barrio, J R and Small, G W and Wong, K P and Huang, S C and Liu, J and Merrill, D A and Giza, C C and Fitzsimmons, R P and Omalu, B and Bailes, J and Kepe, V},
year = {2015},
date = {2015-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {112},
number = {16},
pages = {E2039--47},
abstract = {Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged},
pubstate = {published},
tppubtype = {article}
}
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; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W
Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article
In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks
@article{Bieniek2015,
title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},
author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {6},
pages = {877--889},
abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks},
pubstate = {published},
tppubtype = {article}
}
Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A
Chronic traumatic encephalopathy and athletes Journal Article
In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.
Abstract | BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]
@article{Meehan3rd2015a,
title = {Chronic traumatic encephalopathy and athletes},
author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},
year = {2015},
date = {2015-01-01},
journal = {Neurology},
volume = {85},
number = {17},
pages = {1504--1511},
abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},
keywords = {*Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]},
pubstate = {published},
tppubtype = {article}
}
Stein, T D; Montenigro, P H; Alvarez, V E; Xia, W; Crary, J F; Tripodis, Y; Daneshvar, D H; Mez, J; Solomon, T; Meng, G; Kubilus, C A; Cormier, K A; Meng, S; Babcock, K; Kiernan, P; Murphy, L; Nowinski, C J; Martin, B; Dixon, D; Stern, R A; Cantu, R C; Kowall, N W; McKee, A C
Beta-amyloid deposition in chronic traumatic encephalopathy Journal Article
In: Acta Neuropathologica, vol. 130, no. 1, pp. 21–34, 2015.
Abstract | BibTeX | Tags: *Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]
@article{Stein2015b,
title = {Beta-amyloid deposition in chronic traumatic encephalopathy},
author = {Stein, T D and Montenigro, P H and Alvarez, V E and Xia, W and Crary, J F and Tripodis, Y and Daneshvar, D H and Mez, J and Solomon, T and Meng, G and Kubilus, C A and Cormier, K A and Meng, S and Babcock, K and Kiernan, P and Murphy, L and Nowinski, C J and Martin, B and Dixon, D and Stern, R A and Cantu, R C and Kowall, N W and McKee, A C},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {1},
pages = {21--34},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Abeta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Abeta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Abeta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p \< 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Abeta plaques and those without. Abeta deposition was significantly associated with the presence of the APOE epsilon4 allele (p = 0.035), older age at symptom onset (p \< 0.001), and older age at death (p \< 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43},
keywords = {*Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]},
pubstate = {published},
tppubtype = {article}
}
McKee, A C; Stein, T D; Kiernan, P T; Alvarez, V E
The neuropathology of chronic traumatic encephalopathy Journal Article
In: Brain Pathology, vol. 25, no. 3, pp. 350–364, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]
@article{McKee2015a,
title = {The neuropathology of chronic traumatic encephalopathy},
author = {McKee, A C and Stein, T D and Kiernan, P T and Alvarez, V E},
year = {2015},
date = {2015-01-01},
journal = {Brain Pathology},
volume = {25},
number = {3},
pages = {350--364},
abstract = {Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. Copyright © 2015 International Society of Neuropathology.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]},
pubstate = {published},
tppubtype = {article}
}
Jandial, R; Duenas, M J; Chen, M Y
Neuroanatomy changes with repetitive mild head injury in athletes Journal Article
In: Neurosurgery, vol. 72, no. 6, pp. N20, 2013.
BibTeX | Tags: *Athletes, *Brain Concussion/pa [Pathology], *Brain/pa [Pathology], Humans
@article{Jandial2013,
title = {Neuroanatomy changes with repetitive mild head injury in athletes},
author = {Jandial, R and Duenas, M J and Chen, M Y},
year = {2013},
date = {2013-01-01},
journal = {Neurosurgery},
volume = {72},
number = {6},
pages = {N20},
keywords = {*Athletes, *Brain Concussion/pa [Pathology], *Brain/pa [Pathology], Humans},
pubstate = {published},
tppubtype = {article}
}
Cantu, R C
Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic contact athletes Journal Article
In: World Neurosurgery, vol. 80, no. 6, pp. 792–793, 2013.
BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain/pa [Pathology], *Diffusion Tensor Imaging/mt [Methods], *Neuroimaging/mt [Methods], Humans, Male
@article{Cantu2013,
title = {Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic contact athletes},
author = {Cantu, R C},
year = {2013},
date = {2013-01-01},
journal = {World Neurosurgery},
volume = {80},
number = {6},
pages = {792--793},
keywords = {*Athletic Injuries/pa [Pathology], *Brain/pa [Pathology], *Diffusion Tensor Imaging/mt [Methods], *Neuroimaging/mt [Methods], Humans, Male},
pubstate = {published},
tppubtype = {article}
}
Barrio, J R; Small, G W; Wong, K P; Huang, S C; Liu, J; Merrill, D A; Giza, C C; Fitzsimmons, R P; Omalu, B; Bailes, J; Kepe, V
In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344] Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 16, pp. E2039–47, 2015.
@article{Barrio2015,
title = {In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344]},
author = {Barrio, J R and Small, G W and Wong, K P and Huang, S C and Liu, J and Merrill, D A and Giza, C C and Fitzsimmons, R P and Omalu, B and Bailes, J and Kepe, V},
year = {2015},
date = {2015-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {112},
number = {16},
pages = {E2039--47},
abstract = {Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
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; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W
Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article
In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.
@article{Bieniek2015,
title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},
author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {6},
pages = {877--889},
abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A
Chronic traumatic encephalopathy and athletes Journal Article
In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.
@article{Meehan3rd2015a,
title = {Chronic traumatic encephalopathy and athletes},
author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},
year = {2015},
date = {2015-01-01},
journal = {Neurology},
volume = {85},
number = {17},
pages = {1504--1511},
abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Stein, T D; Montenigro, P H; Alvarez, V E; Xia, W; Crary, J F; Tripodis, Y; Daneshvar, D H; Mez, J; Solomon, T; Meng, G; Kubilus, C A; Cormier, K A; Meng, S; Babcock, K; Kiernan, P; Murphy, L; Nowinski, C J; Martin, B; Dixon, D; Stern, R A; Cantu, R C; Kowall, N W; McKee, A C
Beta-amyloid deposition in chronic traumatic encephalopathy Journal Article
In: Acta Neuropathologica, vol. 130, no. 1, pp. 21–34, 2015.
@article{Stein2015b,
title = {Beta-amyloid deposition in chronic traumatic encephalopathy},
author = {Stein, T D and Montenigro, P H and Alvarez, V E and Xia, W and Crary, J F and Tripodis, Y and Daneshvar, D H and Mez, J and Solomon, T and Meng, G and Kubilus, C A and Cormier, K A and Meng, S and Babcock, K and Kiernan, P and Murphy, L and Nowinski, C J and Martin, B and Dixon, D and Stern, R A and Cantu, R C and Kowall, N W and McKee, A C},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {1},
pages = {21--34},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Abeta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Abeta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Abeta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p \< 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Abeta plaques and those without. Abeta deposition was significantly associated with the presence of the APOE epsilon4 allele (p = 0.035), older age at symptom onset (p \< 0.001), and older age at death (p \< 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
McKee, A C; Stein, T D; Kiernan, P T; Alvarez, V E
The neuropathology of chronic traumatic encephalopathy Journal Article
In: Brain Pathology, vol. 25, no. 3, pp. 350–364, 2015.
@article{McKee2015a,
title = {The neuropathology of chronic traumatic encephalopathy},
author = {McKee, A C and Stein, T D and Kiernan, P T and Alvarez, V E},
year = {2015},
date = {2015-01-01},
journal = {Brain Pathology},
volume = {25},
number = {3},
pages = {350--364},
abstract = {Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. Copyright © 2015 International Society of Neuropathology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Jandial, R; Duenas, M J; Chen, M Y
Neuroanatomy changes with repetitive mild head injury in athletes Journal Article
In: Neurosurgery, vol. 72, no. 6, pp. N20, 2013.
@article{Jandial2013,
title = {Neuroanatomy changes with repetitive mild head injury in athletes},
author = {Jandial, R and Duenas, M J and Chen, M Y},
year = {2013},
date = {2013-01-01},
journal = {Neurosurgery},
volume = {72},
number = {6},
pages = {N20},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cantu, R C
Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic contact athletes Journal Article
In: World Neurosurgery, vol. 80, no. 6, pp. 792–793, 2013.
@article{Cantu2013,
title = {Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic contact athletes},
author = {Cantu, R C},
year = {2013},
date = {2013-01-01},
journal = {World Neurosurgery},
volume = {80},
number = {6},
pages = {792--793},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Barrio, J R; Small, G W; Wong, K P; Huang, S C; Liu, J; Merrill, D A; Giza, C C; Fitzsimmons, R P; Omalu, B; Bailes, J; Kepe, V
In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344] Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 112, no. 16, pp. E2039–47, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged
@article{Barrio2015,
title = {In vivo characterization of chronic traumatic encephalopathy using [F-18]FDDNP PET brain imaging.[Erratum appears in Proc Natl Acad Sci U S A. 2015 Jun 2;112(22):E2981; PMID: 25964344]},
author = {Barrio, J R and Small, G W and Wong, K P and Huang, S C and Liu, J and Merrill, D A and Giza, C C and Fitzsimmons, R P and Omalu, B and Bailes, J and Kepe, V},
year = {2015},
date = {2015-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {112},
number = {16},
pages = {E2039--47},
abstract = {Chronic traumatic encephalopathy (CTE) is an acquired primary tauopathy with a variety of cognitive, behavioral, and motor symptoms linked to cumulative brain damage sustained from single, episodic, or repetitive traumatic brain injury (TBI). No definitive clinical diagnosis for this condition exists. In this work, we used [F-18]FDDNP PET to detect brain patterns of neuropathology distribution in retired professional American football players with suspected CTE (n = 14) and compared results with those of cognitively intact controls (n = 28) and patients with Alzheimer's dementia (AD) (n = 24), a disease that has been cognitively associated with CTE. [F-18]FDDNP PET imaging results in the retired players suggested the presence of neuropathological patterns consistent with models of concussion wherein brainstem white matter tracts undergo early axonal damage and cumulative axonal injuries along subcortical, limbic, and cortical brain circuitries supporting mood, emotions, and behavior. This deposition pattern is distinctively different from the progressive pattern of neuropathology [paired helical filament (PHF)-tau and amyloid-beta] in AD, which typically begins in the medial temporal lobe progressing along the cortical default mode network, with no or minimal involvement of subcortical structures. This particular [F-18]FDDNP PET imaging pattern in cases of suspected CTE also is primarily consistent with PHF-tau distribution observed at autopsy in subjects with a history of mild TBI and autopsy-confirmed diagnosis of CTE.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Brain/ri [Radionuclide Imaging], *Nitriles, *Positron-Emission Tomography, 0 (2-(1-(6-((2-fluoroethyl)(methyl)amino)-2-naphth, 0 (Nitriles), 80 and over, adult, aged, Alzheimer Disease/ri [Radionuclide Imaging], Amygdala/mi [Microbiology], Amygdala/pa [Pathology], autopsy, Case-Control Studies, Chronic/ri [Radionuclide Imaging], Demography, Humans, Male, Mesencephalon/mi [Microbiology], Mesencephalon/pa [Pathology], middle aged},
pubstate = {published},
tppubtype = {article}
}
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; Rademakers, R; Boeve, B F; McKee, A C; Dickson, D W
Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank Journal Article
In: Acta Neuropathologica, vol. 130, no. 6, pp. 877–889, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks
@article{Bieniek2015,
title = {Chronic traumatic encephalopathy pathology in a neurodegenerative disorders brain bank},
author = {Bieniek, K F and Ross, O A and Cormier, K A and Walton, R L and Soto-Ortolaza, A and Johnston, A E and DeSaro, P and Boylan, K B and Graff-Radford, N R and Wszolek, Z K and Rademakers, R and Boeve, B F and McKee, A C and Dickson, D W},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {6},
pages = {877--889},
abstract = {Chronic traumatic encephalopathy (CTE) is a progressive neurodegenerative disorder linked to repetitive traumatic brain injury (TBI) and characterized by deposition of hyperphosphorylated tau at the depths of sulci. We sought to determine the presence of CTE pathology in a brain bank for neurodegenerative disorders for individuals with and without a history of contact sports participation. Available medical records of 1721 men were reviewed for evidence of past history of injury or participation in contact sports. Subsequently, cerebral cortical samples were processed for tau immunohistochemistry in cases with a documented history of sports exposure as well as age- and disease-matched men and women without such exposure. For cases with available frozen tissue, genetic analysis was performed for variants in APOE, MAPT, and TMEM106B. Immunohistochemistry revealed 21 of 66 former athletes had cortical tau pathology consistent with CTE. CTE pathology was not detected in 198 individuals without exposure to contact sports, including 33 individuals with documented single-incident TBI sustained from falls, motor vehicle accidents, domestic violence, or assaults. Among those exposed to contact sports, those with CTE pathology did not differ from those without CTE pathology with respect to noted clinicopathologic features. There were no significant differences in genetic variants for those with CTE pathology, but we observed a slight increase in MAPT H1 haplotype, and there tended to be fewer homozygous carriers of the protective TMEM106B rs3173615 minor allele in those with sports exposure and CTE pathology compared to those without CTE pathology. In conclusion, this study has identified a small, yet significant, subset of individuals with neurodegenerative disorders and concomitant CTE pathology. CTE pathology was only detected in individuals with documented participation in contact sports. Exposure to contact sports was the greatest risk factor for CTE pathology. Future studies addressing clinical correlates of CTE pathology are needed.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/et [Etiology], *Neurodegenerative Diseases/pa [Pathology], 0 (Apolipoproteins E), 0 (MAPT protein, 0 (Membrane Proteins), 0 (Nerve Tissue Proteins), 0 (tau Proteins), 0 (TMEM106B protein, aged, Apolipoproteins E/ge [Genetics], Athletic Injuries/co [Complications], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/et [Etiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Female, human), Humans, immunohistochemistry, Male, Membrane Proteins/ge [Genetics], Nerve Tissue Proteins/ge [Genetics], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Retrospective Studies, tau Proteins/ge [Genetics], tau Proteins/me [Metabolism], Tissue Banks},
pubstate = {published},
tppubtype = {article}
}
Meehan 3rd, W; Mannix, R; Zafonte, R; Pascual-Leone, A
Chronic traumatic encephalopathy and athletes Journal Article
In: Neurology, vol. 85, no. 17, pp. 1504–1511, 2015.
Abstract | BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]
@article{Meehan3rd2015a,
title = {Chronic traumatic encephalopathy and athletes},
author = {{Meehan 3rd}, W and Mannix, R and Zafonte, R and Pascual-Leone, A},
year = {2015},
date = {2015-01-01},
journal = {Neurology},
volume = {85},
number = {17},
pages = {1504--1511},
abstract = {Recent case reports have described athletes previously exposed to repetitive head trauma while participating in contact sports who later in life developed mood disorders, headaches, cognitive difficulties, suicidal ideation, difficulties with speech, and aggressive behavior. Postmortem discoveries show that some of these athletes have pathologic findings that are collectively termed chronic traumatic encephalopathy (CTE). Current hypotheses suggest that concussions or perhaps blows to the head that do not cause the signs and symptoms necessary for making the diagnosis of concussion, so-called subconcussive blows, cause both the clinical and pathologic findings. There are, however, some athletes who participate in contact sports who do not develop the findings ascribed to CTE. Furthermore, there are people who have headaches, mood disorders, cognitive difficulties, suicidal ideation, and other clinical problems who have neither been exposed to repeated head trauma nor possessed the pathologic postmortem findings of those currently diagnosed with CTE. The current lack of prospective data and properly designed case-control studies limits the current understanding of CTE, leading to debate about the causes of the neuropathologic findings and the clinical observations. Given the potential for referral and recall bias in available studies, it remains unclear whether or not the pathologic findings made postmortem cause the presumed neurobehavioral sequela and whether the presumed risk factors, such as sports activity, cerebral concussions, and subconcussive blows, are solely causative of the clinical signs and symptoms. This article discusses the current evidence and the associated limitations. Copyright © 2015 American Academy of Neurology.},
keywords = {*Athletic Injuries/pa [Pathology], *Brain Concussion/pa [Pathology], *Brain Injury, *Brain/pa [Pathology], *Cognition Disorders/pa [Pathology], *Suicidal Ideation, Aggression/px [Psychology], Athletes, Athletic Injuries/co [Complications], Athletic Injuries/px [Psychology], Brain Concussion/co [Complications], Brain Concussion/px [Psychology], Brain Injury, Chronic/et [Etiology], Chronic/pa [Pathology], Chronic/px [Psychology], Cognition Disorders/et [Etiology], Cognition Disorders/px [Psychology], Headache/et [Etiology], Headache/pa [Pathology], Humans, Mood Disorders/et [Etiology], Mood Disorders/pa [Pathology], Mood Disorders/px [Psychology], Speech Disorders/et [Etiology], Speech Disorders/pa [Pathology], Speech Disorders/px [Psychology]},
pubstate = {published},
tppubtype = {article}
}
Stein, T D; Montenigro, P H; Alvarez, V E; Xia, W; Crary, J F; Tripodis, Y; Daneshvar, D H; Mez, J; Solomon, T; Meng, G; Kubilus, C A; Cormier, K A; Meng, S; Babcock, K; Kiernan, P; Murphy, L; Nowinski, C J; Martin, B; Dixon, D; Stern, R A; Cantu, R C; Kowall, N W; McKee, A C
Beta-amyloid deposition in chronic traumatic encephalopathy Journal Article
In: Acta Neuropathologica, vol. 130, no. 1, pp. 21–34, 2015.
Abstract | BibTeX | Tags: *Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]
@article{Stein2015b,
title = {Beta-amyloid deposition in chronic traumatic encephalopathy},
author = {Stein, T D and Montenigro, P H and Alvarez, V E and Xia, W and Crary, J F and Tripodis, Y and Daneshvar, D H and Mez, J and Solomon, T and Meng, G and Kubilus, C A and Cormier, K A and Meng, S and Babcock, K and Kiernan, P and Murphy, L and Nowinski, C J and Martin, B and Dixon, D and Stern, R A and Cantu, R C and Kowall, N W and McKee, A C},
year = {2015},
date = {2015-01-01},
journal = {Acta Neuropathologica},
volume = {130},
number = {1},
pages = {21--34},
abstract = {Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease associated with repetitive mild traumatic brain injury. It is defined pathologically by the abnormal accumulation of tau in a unique pattern that is distinct from other tauopathies, including Alzheimer's disease (AD). Although trauma has been suggested to increase amyloid beta peptide (Abeta) levels, the extent of Abeta deposition in CTE has not been thoroughly characterized. We studied a heterogeneous cohort of deceased athletes and military veterans with neuropathologically diagnosed CTE (n = 114, mean age at death = 60) to test the hypothesis that Abeta deposition is altered in CTE and associated with more severe pathology and worse clinical outcomes. We found that Abeta deposition, either as diffuse or neuritic plaques, was present in 52 % of CTE subjects. Moreover, Abeta deposition in CTE occurred at an accelerated rate and with altered dynamics in CTE compared to a normal aging population (OR = 3.8, p \< 0.001). We also found a clear pathological and clinical dichotomy between those CTE cases with Abeta plaques and those without. Abeta deposition was significantly associated with the presence of the APOE epsilon4 allele (p = 0.035), older age at symptom onset (p \< 0.001), and older age at death (p \< 0.001). In addition, when controlling for age, neuritic plaques were significantly associated with increased CTE tauopathy stage (beta = 2.43},
keywords = {*Amyloid beta-Peptides/me [Metabolism], *Brain Injury, *Brain/pa [Pathology], *Neurodegenerative Diseases/pa [Pathology], *tau Proteins/me [Metabolism], 0 (Amyloid beta-Peptides), 0 (Apolipoprotein E4), 0 (MAPT protein, 0 (tau Proteins), 80 and over, adult, Age Factors, aged, Amyloid/et [Etiology], Amyloid/me [Metabolism], Amyloid/pa [Pathology], Apolipoprotein E4/ge [Genetics], Athletes, Athletic Injuries/ep [Epidemiology], Athletic Injuries/ge [Genetics], Athletic Injuries/me [Metabolism], Athletic Injuries/pa [Pathology], Brain Injury, Brain/me [Metabolism], Chronic/ep [Epidemiology], Chronic/ge [Genetics], Chronic/me [Metabolism], Chronic/pa [Pathology], Cohort Studies, comorbidity, human), Humans, middle aged, Neurodegenerative Diseases/ep [Epidemiology], Neurodegenerative Diseases/ge [Genetics], Neurodegenerative Diseases/me [Metabolism], Plaque, SEVERITY of illness index, veterans, War-Related Injuries/ep [Epidemiology], War-Related Injuries/ge [Genetics], War-Related Injuries/me [Metabolism], War-Related Injuries/pa [Pathology]},
pubstate = {published},
tppubtype = {article}
}
McKee, A C; Stein, T D; Kiernan, P T; Alvarez, V E
The neuropathology of chronic traumatic encephalopathy Journal Article
In: Brain Pathology, vol. 25, no. 3, pp. 350–364, 2015.
Abstract | BibTeX | Tags: *Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]
@article{McKee2015a,
title = {The neuropathology of chronic traumatic encephalopathy},
author = {McKee, A C and Stein, T D and Kiernan, P T and Alvarez, V E},
year = {2015},
date = {2015-01-01},
journal = {Brain Pathology},
volume = {25},
number = {3},
pages = {350--364},
abstract = {Repetitive brain trauma is associated with a progressive neurological deterioration, now termed as chronic traumatic encephalopathy (CTE). Most instances of CTE occur in association with the play of sports, but CTE has also been reported in association with blast injuries and other neurotrauma. Symptoms of CTE include behavioral and mood changes, memory loss, cognitive impairment and dementia. Like many other neurodegenerative diseases, CTE is diagnosed with certainty only by neuropathological examination of brain tissue. CTE is a tauopathy characterized by the deposition of hyperphosphorylated tau (p-tau) protein as neurofibrillary tangles, astrocytic tangles and neurites in striking clusters around small blood vessels of the cortex, typically at the sulcal depths. Severely affected cases show p-tau pathology throughout the brain. Abnormalities in phosphorylated 43kDa TAR DNA-binding protein are found in most cases of CTE; beta-amyloid is identified in 43%, associated with age. Given the importance of sports participation and physical exercise to physical and psychological health as well as disease resilience, it is critical to identify the genetic risk factors for CTE as well as to understand how other variables, such as stress, age at exposure, gender, substance abuse and other exposures, contribute to the development of CTE. Copyright © 2015 International Society of Neuropathology.},
keywords = {*Brain Injury, *Brain/pa [Pathology], *Neuropathology, 0 (DNA-Binding Proteins), 0 (tau Proteins), Brain/me [Metabolism], Chronic/di [Diagnosis], DNA-Binding Proteins/me [Metabolism], Humans, tau Proteins/me [Metabolism]},
pubstate = {published},
tppubtype = {article}
}
Jandial, R; Duenas, M J; Chen, M Y
Neuroanatomy changes with repetitive mild head injury in athletes Journal Article
In: Neurosurgery, vol. 72, no. 6, pp. N20, 2013.
BibTeX | Tags: *Athletes, *Brain Concussion/pa [Pathology], *Brain/pa [Pathology], Humans
@article{Jandial2013,
title = {Neuroanatomy changes with repetitive mild head injury in athletes},
author = {Jandial, R and Duenas, M J and Chen, M Y},
year = {2013},
date = {2013-01-01},
journal = {Neurosurgery},
volume = {72},
number = {6},
pages = {N20},
keywords = {*Athletes, *Brain Concussion/pa [Pathology], *Brain/pa [Pathology], Humans},
pubstate = {published},
tppubtype = {article}
}
Cantu, R C
Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic contact athletes Journal Article
In: World Neurosurgery, vol. 80, no. 6, pp. 792–793, 2013.
BibTeX | Tags: *Athletic Injuries/pa [Pathology], *Brain/pa [Pathology], *Diffusion Tensor Imaging/mt [Methods], *Neuroimaging/mt [Methods], Humans, Male
@article{Cantu2013,
title = {Role of diffusion tensor imaging MRI in detecting brain injury in asymptomatic contact athletes},
author = {Cantu, R C},
year = {2013},
date = {2013-01-01},
journal = {World Neurosurgery},
volume = {80},
number = {6},
pages = {792--793},
keywords = {*Athletic Injuries/pa [Pathology], *Brain/pa [Pathology], *Diffusion Tensor Imaging/mt [Methods], *Neuroimaging/mt [Methods], Humans, Male},
pubstate = {published},
tppubtype = {article}
}