@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.}",
note = "Funding Information: We thank C. Acker for help with Sandwich ELISA and P. Davies (Litwin Zucker Center for Alzheimer's Research, Feinstein Institute, New York, USA) for providing tau antibodies. We thank K. Jansen-West, E. Perkerson and L. Petrucelli (Mayo Clinic Jacksonville) for providing additional tau viruses and D. Sulzer for discussions regarding cell electrophysiology. We also thank L. Liu for assistance with mouse tissue collection, C. Profaci for assistance with optogenetic experiments and L. Shi for administrative assistance. This work was supported by a BrightFocus Foundation fellowship to J.W., NIH/NINDS grants NS081555 and NS074874 to K.E.D., Cure Alzheimer's Fund to K.E.D., the Parkinson's Disease Foundation to D.S and NIH/NIA grant AG050425 to S.A.H. and K.E.D. A.M. is supported by funds from NIH/NIA AA19801. S.W. is supported by the NIHR Queen Square Dementia Biomedical Research Unit. Publisher Copyright: {\textcopyright} 2016 Nature America, Inc.",
year = "2016",
month = aug,
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",
}