Evidence map›Paper›PMID 29042562›Full record

ArticleNature communications2017

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 and 10 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
97citing papers in PubMed, 2 pooled it
10.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

97 citing papers in PubMed, 2 syntheses or guidelines pooled it, 150 citations in OpenAlex.

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37 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 8 institutions in 2 countries.

Onder AlbayramDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0002-2028-1458
Asami KondoDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA.
Rebekah MannixDivision of Emergency Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115, USA.
Colin SmithDepartment of Neuropathology, University of Edinburgh, 49 Little France Crescent, Edinburgh, EH16 4SB, UK.
Cheng-Yu TsaiDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA.
Chenyu LiDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA.
Megan K HerbertDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA.ORCID http://orcid.org/0000-0003-1599-4362
Jianhua QiuDivision of Emergency Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115, USA.
Michael MonuteauxDivision of Emergency Medicine, Children's Hospital Boston, Harvard Medical School, 300 Longwood Ave, Boston, MA, 02115, USA.
Jane DriverDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA.
Sandra YanDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
William GormleyDepartment of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA.
Ava M PuccioDepartment of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA, 15213, USA.
David O OkonkwoDepartment of Neurosurgery, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA, 15213, USA.
Brandon Lucke-WoldDepartment of Neurosurgery, West Virginia University, Suite 4300, Health Sciences Center, PO Box 9183, Morgantown, WV, 26506, USA.
Julian BailesDepartment of Neurosurgery, NorthShore University Health System, University of Chicago, Pritzker School of Medicine, 3rd Floor Kellogg, Evanston, IL, 60637, USA.
William MeehanMicheli Center for Sports Injury Prevention, Division of Sports Medicine, Children's Hospital Boston, Harvard Medical School, 319 Longwood Avenue, Boston, MA, 02115, USA.
Mark ZeidelDepartment of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.
Kun Ping LuDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA. klu@bidmc.harvard.edu.
Xiao Zhen ZhouDivision of Translational Therapeutics, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 0408, Boston, MA, 02215, USA. zhou@bidmc.harvard.edu.
Beth Israel Deaconess Medical Center · USBoston Children's Hospital · USBrigham and Women's Hospital · USUniversity of Pittsburgh Medical Center · USHarvard University · USNorthShore University HealthSystem · USUniversity of Edinburgh · GBWest Virginia University · US

Funding

Development of Therapeutic Antibody for Traumatic Brain InjuryU01NS096835 · NINDS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI ZEIDEL, MARK L. · 2017 to 2021
$5.1M
RESEARCH TRAINING IN PEDIATRIC EMERGENCY MEDICINET32HD040128 · NICHD · CHILDREN'S HOSPITAL BOSTON · PI Kenneth D. Mandl · 2001 to 2026
$5.0M
Conformational Dynamics in Pin1 REgulation of APP Processing and Abeta ProductionR01AG029385 · NIA · CORNELL UNIVERSITY · PI NICHOLSON, LINDA K · 2007 to 2011
$2.3M
Function and Regulation of the Phosphorylation-Specific Prolyl Isomerase Pin1R01CA167677 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LU, KUN PING · 2012 to 2016
$1.9M
Drug Discovery against the Early, Secreted and Toxic Tau in Alzheimer's DiseaseR01AG046319 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LU, KUN PING · 2014 to 2018
$1.8M
NCI NIH HHS R01 CA167677NIA NIH HHS R01 AG029385NIA NIH HHS R01 AG046319NICHD NIH HHS T32 HD040128NINDS NIH HHS U01 NS096835
6 · The paper itself

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.Induction of the cis form of phosphorylated tau (cis P-tau) has previously been shown to occur in animal models of traumatic brain injury (TBI), and blocking this form of tau using antibody was beneficial in a rodent model of severe TBI. Here the authors show that cis P-tau induction is a feature of several different forms of TBI in humans, and that administration of cis P-tau targeting antibody to rodents reduces or delays pathological features of TBI.

Indexed as

Disease Models, AnimalAdolescentAdultAgedAnimalsAntibodies, NeutralizingAxonsBrainBrain InjuriesCell Line, TumorFemaleHumansMaleMice, Inbred C57BLMiddle AgedMotor ActivityAntibodies, Neutralizingtau Proteins

Identifiers

PMID29042562
PMCPMC5645414
OpenAlexW2762474536

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.