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Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae

Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and associated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer’s disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology an...

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Autores principales: Albayram, Onder, Kondo, Asami, Mannix, Rebekah, Smith, Colin, Tsai, Cheng-Yu, Li, Chenyu, Herbert, Megan K., Qiu, Jianhua, Monuteaux, Michael, Driver, Jane, Yan, Sandra, Gormley, William, Puccio, Ava M., Okonkwo, David O., Lucke-Wold, Brandon, Bailes, Julian, Meehan, William, Zeidel, Mark, Lu, Kun Ping, Zhou, Xiao Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645414/
https://www.ncbi.nlm.nih.gov/pubmed/29042562
http://dx.doi.org/10.1038/s41467-017-01068-4
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author Albayram, Onder
Kondo, Asami
Mannix, Rebekah
Smith, Colin
Tsai, Cheng-Yu
Li, Chenyu
Herbert, Megan K.
Qiu, Jianhua
Monuteaux, Michael
Driver, Jane
Yan, Sandra
Gormley, William
Puccio, Ava M.
Okonkwo, David O.
Lucke-Wold, Brandon
Bailes, Julian
Meehan, William
Zeidel, Mark
Lu, Kun Ping
Zhou, Xiao Zhen
author_facet Albayram, Onder
Kondo, Asami
Mannix, Rebekah
Smith, Colin
Tsai, Cheng-Yu
Li, Chenyu
Herbert, Megan K.
Qiu, Jianhua
Monuteaux, Michael
Driver, Jane
Yan, Sandra
Gormley, William
Puccio, Ava M.
Okonkwo, David O.
Lucke-Wold, Brandon
Bailes, Julian
Meehan, William
Zeidel, Mark
Lu, Kun Ping
Zhou, Xiao Zhen
author_sort Albayram, Onder
collection PubMed
description Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and associated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer’s disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment.
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spelling pubmed-56454142017-10-19 Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae Albayram, Onder Kondo, Asami Mannix, Rebekah Smith, Colin Tsai, Cheng-Yu Li, Chenyu Herbert, Megan K. Qiu, Jianhua Monuteaux, Michael Driver, Jane Yan, Sandra Gormley, William Puccio, Ava M. Okonkwo, David O. Lucke-Wold, Brandon Bailes, Julian Meehan, William Zeidel, Mark Lu, Kun Ping Zhou, Xiao Zhen Nat Commun Article Traumatic brain injury (TBI) is characterized by acute neurological dysfunction and associated with the development of chronic traumatic encephalopathy (CTE) and Alzheimer’s disease. We previously showed that cis phosphorylated tau (cis P-tau), but not the trans form, contributes to tau pathology and functional impairment in an animal model of severe TBI. Here we found that in human samples obtained post TBI due to a variety of causes, cis P-tau is induced in cortical axons and cerebrospinal fluid and positively correlates with axonal injury and clinical outcome. Using mouse models of severe or repetitive TBI, we showed that cis P-tau elimination with a specific neutralizing antibody administered immediately or at delayed time points after injury, attenuates the development of neuropathology and brain dysfunction during acute and chronic phases including CTE-like pathology and dysfunction after repetitive TBI. Thus, cis P-tau contributes to short-term and long-term sequelae after TBI, but is effectively neutralized by cis antibody treatment. Nature Publishing Group UK 2017-10-17 /pmc/articles/PMC5645414/ /pubmed/29042562 http://dx.doi.org/10.1038/s41467-017-01068-4 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Albayram, Onder
Kondo, Asami
Mannix, Rebekah
Smith, Colin
Tsai, Cheng-Yu
Li, Chenyu
Herbert, Megan K.
Qiu, Jianhua
Monuteaux, Michael
Driver, Jane
Yan, Sandra
Gormley, William
Puccio, Ava M.
Okonkwo, David O.
Lucke-Wold, Brandon
Bailes, Julian
Meehan, William
Zeidel, Mark
Lu, Kun Ping
Zhou, Xiao Zhen
Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
title Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
title_full Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
title_fullStr Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
title_full_unstemmed Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
title_short Cis P-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
title_sort cis p-tau is induced in clinical and preclinical brain injury and contributes to post-injury sequelae
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5645414/
https://www.ncbi.nlm.nih.gov/pubmed/29042562
http://dx.doi.org/10.1038/s41467-017-01068-4
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