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

Onder Albayram, Asami Kondo, Rebekah Mannix, Colin Smith, Cheng-Yu Tsai, Chenyu Li, Megan K. Herbert, Jianhua Qiu, Michael Monuteaux, Jane Driver, Sandra Yan, William Gormley, Ava M. Puccio, David O. Okonkwo, Brandon Lucke-Wold, Julian Bailes, William Meehan, Mark Zeidel, Kun Ping Lu () and Xiao Zhen Zhou ()
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Onder Albayram: Harvard Medical School
Asami Kondo: Harvard Medical School
Rebekah Mannix: Harvard Medical School
Colin Smith: University of Edinburgh
Cheng-Yu Tsai: Harvard Medical School
Chenyu Li: Harvard Medical School
Megan K. Herbert: Harvard Medical School
Jianhua Qiu: Harvard Medical School
Michael Monuteaux: Harvard Medical School
Jane Driver: Harvard Medical School
Sandra Yan: Harvard Medical School
William Gormley: Harvard Medical School
Ava M. Puccio: University of Pittsburgh Medical Center
David O. Okonkwo: University of Pittsburgh Medical Center
Brandon Lucke-Wold: West Virginia University
Julian Bailes: University of Chicago, Pritzker School of Medicine
William Meehan: Harvard Medical School
Mark Zeidel: Harvard Medical School
Kun Ping Lu: Harvard Medical School
Xiao Zhen Zhou: Harvard Medical School

Nature Communications, 2017, vol. 8, issue 1, 1-17

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-01068-4

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