Induction of a transmissible tau pathology by traumatic brain injury

Elisa R Zanier, Ilaria Bertani, Eliana Sammali, Francesca Pischiutta, Maria Antonietta Chiaravalloti, Gloria Vegliante, Antonio Masone, Alessandro Corbelli, Douglas H Smith, David K Menon, Nino Stocchetti, Fabio Fiordaliso, Maria-Grazia De Simoni, William Stewart, Roberto Chiesa

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)2685-2699
Number of pages15
JournalBrain : a journal of neurology
Volume141
Issue number9
DOIs
Publication statusPublished - Sep 1 2018

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Pathology
Tauopathies
Memory Disorders
Wounds and Injuries
Neurodegenerative Diseases
Cerebral Cortex
Hippocampus
Traumatic Brain Injury
Brain

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Zanier, E. R., Bertani, I., Sammali, E., Pischiutta, F., Chiaravalloti, M. A., Vegliante, G., ... Chiesa, R. (2018). Induction of a transmissible tau pathology by traumatic brain injury. Brain : a journal of neurology, 141(9), 2685-2699. https://doi.org/10.1093/brain/awy193

Induction of a transmissible tau pathology by traumatic brain injury. / Zanier, Elisa R; Bertani, Ilaria; Sammali, Eliana; Pischiutta, Francesca; Chiaravalloti, Maria Antonietta; Vegliante, Gloria; Masone, Antonio; Corbelli, Alessandro; Smith, Douglas H; Menon, David K; Stocchetti, Nino; Fiordaliso, Fabio; De Simoni, Maria-Grazia; Stewart, William; Chiesa, Roberto.

In: Brain : a journal of neurology, Vol. 141, No. 9, 01.09.2018, p. 2685-2699.

Research output: Contribution to journalArticle

Zanier, ER, Bertani, I, Sammali, E, Pischiutta, F, Chiaravalloti, MA, Vegliante, G, Masone, A, Corbelli, A, Smith, DH, Menon, DK, Stocchetti, N, Fiordaliso, F, De Simoni, M-G, Stewart, W & Chiesa, R 2018, 'Induction of a transmissible tau pathology by traumatic brain injury', Brain : a journal of neurology, vol. 141, no. 9, pp. 2685-2699. https://doi.org/10.1093/brain/awy193
Zanier ER, Bertani I, Sammali E, Pischiutta F, Chiaravalloti MA, Vegliante G et al. Induction of a transmissible tau pathology by traumatic brain injury. Brain : a journal of neurology. 2018 Sep 1;141(9):2685-2699. https://doi.org/10.1093/brain/awy193
Zanier, Elisa R ; Bertani, Ilaria ; Sammali, Eliana ; Pischiutta, Francesca ; Chiaravalloti, Maria Antonietta ; Vegliante, Gloria ; Masone, Antonio ; Corbelli, Alessandro ; Smith, Douglas H ; Menon, David K ; Stocchetti, Nino ; Fiordaliso, Fabio ; De Simoni, Maria-Grazia ; Stewart, William ; Chiesa, Roberto. / Induction of a transmissible tau pathology by traumatic brain injury. In: Brain : a journal of neurology. 2018 ; Vol. 141, No. 9. pp. 2685-2699.
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