Induction of a transmissible tau pathology by traumatic brain injury.


Type
Article
Change log
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)