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

142 Citations (Scopus)

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

Fingerprint

Tauopathies
Alzheimer Disease
Optogenetics
Pathology
tau Proteins
Extracellular Space
Tissue Donors
Neurons
Brain
Therapeutics
In Vitro Techniques

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Wu, J. W., Hussaini, S. A., Bastille, I. M., Rodriguez, G. A., Mrejeru, A., Rilett, K., ... 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

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

In: Nature Neuroscience, Vol. 19, No. 8, 01.08.2016, p. 1085-1092.

Research output: Contribution to journalArticle

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
Wu JW, Hussaini SA, Bastille IM, Rodriguez GA, Mrejeru A, Rilett K et al. Neuronal activity enhances tau propagation and tau pathology in vivo. Nature Neuroscience. 2016 Aug 1;19(8):1085-1092. https://doi.org/10.1038/nn.4328
Wu, Jessica W. ; Hussaini, S. Abid ; Bastille, Isle M. ; Rodriguez, Gustavo A. ; Mrejeru, Ana ; Rilett, Kelly ; Sanders, David W. ; Cook, Casey ; Fu, Hongjun ; Boonen, Rick A C M ; Herman, Mathieu ; Nahmani, Eden ; Emrani, Sheina ; Figueroa, Y. Helen ; Diamond, Marc I. ; Clelland, Catherine L. ; Wray, Selina ; Duff, Karen E. / Neuronal activity enhances tau propagation and tau pathology in vivo. In: Nature Neuroscience. 2016 ; Vol. 19, No. 8. pp. 1085-1092.
@article{33eeefaf81c14f5fa011eaec1db732cd,
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.}",
year = "2016",
month = "8",
day = "1",
doi = "10.1038/nn.4328",
language = "English (US)",
volume = "19",
pages = "1085--1092",
journal = "Nature Neuroscience",
issn = "1097-6256",
publisher = "Nature Publishing Group",
number = "8",

}

TY - JOUR

T1 - Neuronal activity enhances tau propagation and tau pathology in vivo

AU - Wu, Jessica W.

AU - Hussaini, S. Abid

AU - Bastille, Isle M.

AU - Rodriguez, Gustavo A.

AU - Mrejeru, Ana

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

AU - Diamond, Marc I.

AU - Clelland, Catherine L.

AU - Wray, Selina

AU - Duff, Karen E.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=84975222113&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975222113&partnerID=8YFLogxK

U2 - 10.1038/nn.4328

DO - 10.1038/nn.4328

M3 - Article

VL - 19

SP - 1085

EP - 1092

JO - Nature Neuroscience

JF - Nature Neuroscience

SN - 1097-6256

IS - 8

ER -