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, Xiao Zhen Zhou

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number1000
Number of pages17
JournalNature Communications
Volume8
DOIs
Publication statusPublished - 17 Oct 2017

Keywords

  • PROLYL ISOMERASE PIN1
  • CLOSED-HEAD INJURY
  • CHRONIC TRAUMATIC ENCEPHALOPATHY
  • DIFFUSE AXONAL INJURY
  • ALZHEIMERS-DISEASE
  • COGNITIVE DEFICITS
  • PHOSPHORYLATED TAU
  • EXPERIMENTAL-MODEL
  • UNITED-STATES
  • MOTOR-SKILLS

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