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

doi:10.1038/nn.4328

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

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497 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 language	English (US)
Pages (from-to)	1085-1092
Number of pages	8
Journal	Nature neuroscience
Volume	19
Issue number	8
DOIs	https://doi.org/10.1038/nn.4328
State	Published - Aug 1 2016

ASJC Scopus subject areas

General Neuroscience

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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

Wu, JW, Hussaini, SA, Bastille, IM, Rodriguez, GA, Mrejeru, A, Rilett, K, Sanders, DW, Cook, C, Fu, H, Boonen, RACM, Herman, M, Nahmani, E, Emrani, S, Figueroa, YH, Diamond, MI, Clelland, CL, Wray, S & Duff, KE 2016, 'Neuronal activity enhances tau propagation and tau pathology in vivo', Nature neuroscience, vol. 19, no. 8, pp. 1085-1092. https://doi.org/10.1038/nn.4328

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title = "Neuronal activity enhances tau propagation and tau pathology in vivo",

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.",

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

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AU - Rilett, Kelly

AU - Sanders, David W.

AU - Cook, Casey

AU - Fu, Hongjun

AU - Boonen, Rick A C M

AU - Herman, Mathieu

AU - Nahmani, Eden

AU - Emrani, Sheina

AU - Figueroa, Y. Helen

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AU - Clelland, Catherine L.

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AB - 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.

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Neuronal activity enhances tau propagation and tau pathology in vivo

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