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Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.

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Title: Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.
Authors: Kondo, Asami, Shahpasand, Koorosh, Mannix, Rebekah, Qiu, Jianhua, Moncaster, Juliet, Chen, Chun-Hau, Yao, Yandan, Lin, Yu-Min, Driver, Jane A., Sun, Yan, Wei, Shuo, Luo, Man-Li, Albayram, Onder, Huang, Pengyu, Rotenberg, Alexander, Ryo, Akihide, Goldstein, Lee E., Pascual-Leone, Alvaro, McKee, Ann C., Meehan, William
Source: Nature. 7/23/2015, Vol. 523 Issue 7561, p431-436. 6p. 1 Diagram, 2 Charts, 13 Graphs.
Subjects: Brain injuries, Neurodegeneration, Chronic traumatic encephalopathy, Alzheimer's disease, Tau proteins, Pathology
Abstract: Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer's disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term 'cistauosis', appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer's disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury. [ABSTRACT FROM AUTHOR]
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: Antibody against early driver of neurodegeneration cis P-tau blocks brain injury and tauopathy.
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  Data: <searchLink fieldCode="AR" term="%22Kondo%2C+Asami%22">Kondo, Asami</searchLink><br /><searchLink fieldCode="AR" term="%22Shahpasand%2C+Koorosh%22">Shahpasand, Koorosh</searchLink><br /><searchLink fieldCode="AR" term="%22Mannix%2C+Rebekah%22">Mannix, Rebekah</searchLink><br /><searchLink fieldCode="AR" term="%22Qiu%2C+Jianhua%22">Qiu, Jianhua</searchLink><br /><searchLink fieldCode="AR" term="%22Moncaster%2C+Juliet%22">Moncaster, Juliet</searchLink><br /><searchLink fieldCode="AR" term="%22Chen%2C+Chun-Hau%22">Chen, Chun-Hau</searchLink><br /><searchLink fieldCode="AR" term="%22Yao%2C+Yandan%22">Yao, Yandan</searchLink><br /><searchLink fieldCode="AR" term="%22Lin%2C+Yu-Min%22">Lin, Yu-Min</searchLink><br /><searchLink fieldCode="AR" term="%22Driver%2C+Jane+A%2E%22">Driver, Jane A.</searchLink><br /><searchLink fieldCode="AR" term="%22Sun%2C+Yan%22">Sun, Yan</searchLink><br /><searchLink fieldCode="AR" term="%22Wei%2C+Shuo%22">Wei, Shuo</searchLink><br /><searchLink fieldCode="AR" term="%22Luo%2C+Man-Li%22">Luo, Man-Li</searchLink><br /><searchLink fieldCode="AR" term="%22Albayram%2C+Onder%22">Albayram, Onder</searchLink><br /><searchLink fieldCode="AR" term="%22Huang%2C+Pengyu%22">Huang, Pengyu</searchLink><br /><searchLink fieldCode="AR" term="%22Rotenberg%2C+Alexander%22">Rotenberg, Alexander</searchLink><br /><searchLink fieldCode="AR" term="%22Ryo%2C+Akihide%22">Ryo, Akihide</searchLink><br /><searchLink fieldCode="AR" term="%22Goldstein%2C+Lee+E%2E%22">Goldstein, Lee E.</searchLink><br /><searchLink fieldCode="AR" term="%22Pascual-Leone%2C+Alvaro%22">Pascual-Leone, Alvaro</searchLink><br /><searchLink fieldCode="AR" term="%22McKee%2C+Ann+C%2E%22">McKee, Ann C.</searchLink><br /><searchLink fieldCode="AR" term="%22Meehan%2C+William%22">Meehan, William</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Nature%22">Nature</searchLink>. 7/23/2015, Vol. 523 Issue 7561, p431-436. 6p. 1 Diagram, 2 Charts, 13 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Brain+injuries%22">Brain injuries</searchLink><br /><searchLink fieldCode="DE" term="%22Neurodegeneration%22">Neurodegeneration</searchLink><br /><searchLink fieldCode="DE" term="%22Chronic+traumatic+encephalopathy%22">Chronic traumatic encephalopathy</searchLink><br /><searchLink fieldCode="DE" term="%22Alzheimer's+disease%22">Alzheimer's disease</searchLink><br /><searchLink fieldCode="DE" term="%22Tau+proteins%22">Tau proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Pathology%22">Pathology</searchLink>
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  Data: Traumatic brain injury (TBI), characterized by acute neurological dysfunction, is one of the best known environmental risk factors for chronic traumatic encephalopathy and Alzheimer's disease, the defining pathologic features of which include tauopathy made of phosphorylated tau protein (P-tau). However, tauopathy has not been detected in the early stages after TBI, and how TBI leads to tauopathy is unknown. Here we find robust cis P-tau pathology after TBI in humans and mice. After TBI in mice and stress in vitro, neurons acutely produce cis P-tau, which disrupts axonal microtubule networks and mitochondrial transport, spreads to other neurons, and leads to apoptosis. This process, which we term 'cistauosis', appears long before other tauopathy. Treating TBI mice with cis antibody blocks cistauosis, prevents tauopathy development and spread, and restores many TBI-related structural and functional sequelae. Thus, cis P-tau is a major early driver of disease after TBI and leads to tauopathy in chronic traumatic encephalopathy and Alzheimer's disease. The cis antibody may be further developed to detect and treat TBI, and prevent progressive neurodegeneration after injury. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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