Neuronal activity enhances tau propagation and tau pathology in vivo

Jessica W. Wu, S. Abid Hussaini, Isle M. Bastille, Gustavo A. Rodriguez, Ana Mrejeru, Kelly Rilett, David W. Sanders, Casey Cook, Hongjun Fu, Rick A C M Boonen, Mathieu Herman, Eden Nahmani, Sheina Emrani, Y. Helen Figueroa, Marc I. Diamond, Catherine L. Clelland, Selina Wray, Karen E. Duff

Research output: Contribution to journalArticle

191 Scopus citations

Abstract

Tau protein can transfer between neurons transneuronally and trans-synaptically, which is thought to explain the progressive spread of tauopathy observed in the brain of patients with Alzheimer's disease. Here we show that physiological tau released from donor cells can transfer to recipient cells via the medium, suggesting that at least one mechanism by which tau can transfer is via the extracellular space. Neuronal activity has been shown to regulate tau secretion, but its effect on tau pathology is unknown. Using optogenetic and chemogenetic approaches, we found that increased neuronal activity stimulates the release of tau in vitro and enhances tau pathology in vivo. These data have implications for disease pathogenesis and therapeutic strategies for Alzheimer's disease and other tauopathies.

Original languageEnglish (US)
Pages (from-to)1085-1092
Number of pages8
JournalNature Neuroscience
Volume19
Issue number8
DOIs
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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    Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., Sanders, D. W., Cook, C., Fu, H., Boonen, R. A. C. M., Herman, M., Nahmani, E., Emrani, S., Figueroa, Y. H., Diamond, M. I., Clelland, C. L., Wray, S., & Duff, K. E. (2016). Neuronal activity enhances tau propagation and tau pathology in vivo. Nature Neuroscience, 19(8), 1085-1092. https://doi.org/10.1038/nn.4328