Induction of a transmissible tau pathology by traumatic brain injury

Zanier, E. R. et al. (2018) Induction of a transmissible tau pathology by traumatic brain injury. Brain, 141(9), pp. 2685-2699. (doi: 10.1093/brain/awy193) (PMID:30084913) (PMCID:PMC6113646)

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Traumatic brain injury is a risk factor for subsequent neurodegenerative disease, including chronic traumatic encephalopathy, a tauopathy mostly associated with repetitive concussion and blast, but not well recognized as a consequence of severe traumatic brain injury. Here we show that a single severe brain trauma is associated with the emergence of widespread hyperphosphorylated tau pathology in a proportion of humans surviving late after injury. In parallel experimental studies, in a model of severe traumatic brain injury in wild-type mice, we found progressive and widespread tau pathology, replicating the findings in humans. Brain homogenates from these mice, when inoculated into the hippocampus and overlying cerebral cortex of naive mice, induced widespread tau pathology, synaptic loss, and persistent memory deficits. These data provide evidence that experimental brain trauma induces a self-propagating tau pathology, which can be transmitted between mice, and call for future studies aimed at investigating the potential transmissibility of trauma associated tau pathology in humans.

Item Type:Articles
Additional Information:This work was supported by the National Institutes of Health (NIH NS094003 and NS038104) (DHS, WS); by NHS Research Scotland Career- Researcher Fellowship (WS); and the Alzheimer’s Association (AARG-18-532633) (ERZ, RC); DKM was supported by a Senior Investigator award from the National Institute for Health Research (UK).
Glasgow Author(s) Enlighten ID:Stewart, Dr William
Authors: Zanier, E. R., Bertani, I., Sammali, E., Pischiutta, F., Chiaravalloti, M. A., Vegliante, G., Masone, A., Corbelli, A., Smith, D. H., Menon, D. K., Stocchetti, N., Fiordaliso, F., De Simoni, M.-G., Stewart, W., and Chiesa, R.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Brain
Publisher:Oxford University Press
ISSN (Online):1460-2156
Published Online:01 August 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Brain 141(9): 2685-2699
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
696421Characterising amyloid pathologies after traumatic brain injuryWilliam StewartNational Institute of Health (NIH-BETH)2R01NS038104-15A1RI NEUROSCIENCE & PSYCHOLOGY