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Induction of a transmissible tau pathology by traumatic brain injury.

Accepted version
Peer-reviewed

Type

Article

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Authors

Zanier, Elisa R 
Bertani, Ilaria 
Sammali, Eliana 
Pischiutta, Francesca 
Chiaravalloti, Maria Antonietta 

Abstract

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 naïve 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.

Description

Keywords

Aged, Aged, 80 and over, Animals, Brain, Brain Concussion, Brain Injuries, Traumatic, Cerebral Cortex, Disease Models, Animal, Humans, Male, Mice, Mice, Inbred C57BL, Middle Aged, Neurodegenerative Diseases, Phosphorylation, Tauopathies, tau Proteins

Journal Title

Brain

Conference Name

Journal ISSN

0006-8950
1460-2156

Volume Title

141

Publisher

Oxford University Press (OUP)