TDP-43 Proteinopathy and Motor Neuron Disease in Chronic Traumatic Encephalopathy
Ann C. McKee,Brandon E. Gavett,Robert S. Stern,Christopher J. Nowinski,Robert C. Cantu,Neil W. Kowall,Daniel P. Perl,E. Tessa Hedley-Whyte,Bruce H. Price,Christopher P. Sullivan,Peter J. Morin,H. J. Lee,Caroline A. Kubilus,Daniel H. Daneshvar,Megan Wulff,Andrew E. Budson +15 more
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TLDR
This work has found the first pathological evidence that repetitive head trauma experienced in collision sports might be associated with the development of a motor neuron disease.Abstract:
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.read more
Citations
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Journal ArticleDOI
Consensus statement on Concussion in Sport - The 4th International Conference on Concussion in Sport held in Zurich, November 2012
Paul McCrory,Willem H. Meeuwisse,Mark Aubry,Bob Cantu,Jiří Dvořák,Ruben J. Echemendia,Lars Engebretsen,Lars Engebretsen,Karen M. Johnston,Jeff Kutcher,Martin Raftery,Allen K. Sills,Brian W. Benson,Gavin A Davis,Richard G. Ellenbogen,Kevin M. Guskiewicz,Stanley A. Herring,Grant L. Iverson,Barry D. Jordan,Barry D. Jordan,James Kissick,Michael McCrea,Andrew S. McIntosh,Andrew S. McIntosh,David Maddocks,Michael Makdissi,Michael Makdissi,Laura Purcell,Margot Putukian,Margot Putukian,Kathryn J Schneider,Charles H. Tator,Michael Turner +32 more
TL;DR: The 4th International Conference on Concussion in Sport held in Zurich, November 2012 was attended by Paul McCrory, Willem H Meeuwisse, Mark Aubry, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills and Kathryn Schneider.
Journal ArticleDOI
Consensus statement on concussion in sport
Paul McCrory,Willem H. Meeuwisse,Mark Aubry,Bob Cantu,Jiří Dvořák,Ruben J. Echemendia,Lars Engebretsen,Karen M. Johnston,Jeffrey S. Kutcher,Martin Raftery,Allen Sills,Brian W. Benson,Gavin A Davis,Richard G. Ellenbogen,Kevin M. Guskiewicz,Stanley A. Herring,Grant L. Iverson,Barry D. Jordan,James Kissick,Michael McCrea,Andrew S. McIntosh,David Maddocks,Michael Makdissi,Laura Purcell,Margot Putukian,Kathryn J Schneider,Charles H. Tator,Michael Turner +27 more
TL;DR: This paper is a revision and update of the recommendations developed following the 1st (Vienna 2001), 2nd (Prague 2004) and 3rd (Zurich 2008) International Consensus Conferences on Concussions in Sport and is based on the deliberations at the 4th International Conference on Concussion in Sport held in Zurich, November 2012.
Journal ArticleDOI
The spectrum of disease in chronic traumatic encephalopathy
Ann C. McKee,Thor D. Stein,Thor D. Stein,Christopher J. Nowinski,Robert S. Stern,Daniel H. Daneshvar,Victor E. Alvarez,H. J. Lee,Garth F. Hall,Sydney M. Wojtowicz,Sydney M. Wojtowicz,Christine M. Baugh,David O. Riley,Caroline A. Kubilus,Kerry Cormier,Matthew A. Jacobs,Brett Martin,Carmela R. Abraham,Tsuneya Ikezu,Robert Ross Reichard,Benjamin Wolozin,Andrew E. Budson,Andrew E. Budson,Lee E. Goldstein,Neil W. Kowall,Robert C. Cantu +25 more
TL;DR: The frequent association of chronic traumatic encephalopathy with other neurodegenerative disorders suggests that repetitive brain trauma and hyperphosphorylated tau protein deposition promote the accumulation of other abnormally aggregated proteins including TAR DNA-binding protein 43, amyloid beta protein and alpha-synuclein.
Journal ArticleDOI
Consensus statement on concussion in sport--the 4th International Conference on Concussion in Sport held in Zurich, November 2012.
Paul McCrory,Willem H. Meeuwisse,Karen M. Johnston,Jiri Dvorak,Mark Aubry,Mick Molloy,Robert C. Cantu +6 more
TL;DR: The 4th International Conference on Concussion in Sport held in Zurich, November 2012 was attended by Paul McCrory, Willem H Meeuwisse, Mark Aubry, Jiří Dvořák, Ruben J Echemendia, Lars Engebretsen, Karen Johnston, Jeffrey S Kutcher, Martin Raftery, Allen Sills and Kathryn Schneider.
International Conference on Concussion in Sport Held in Zurich, November 2012
Paul McCrory,Willem H. Meeuwisse,Mark Aubry,Bob Cantu,Ruben J. Echemendia,Lars Engebretsen,Karen M. Johnston,Jeffrey S. Kutcher,Martin Raftery,Allen K. Sills,Brian W. Benson,Gavin A Davis,Richard Ellenbogan,Kevin M. Guskiewicz,Stanley A. Herring,Grant L. Iverson,Barry D. Jordan,James Kissick,Michael McCrea,Andrew S. McIntosh,David Maddocks,Michael Makdissi,Laura Purcell,Margot Putukian,Kathryn J Schneider,Charles H. Tator,Michael A. Turner +26 more
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