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Neuronal activity enhances tau propagation and tau pathology in vivo

Wu, JW; Hussaini, SA; Bastille, IM; Rodriguez, GA; Mrejeru, A; Rilett, K; Sanders, DW; ... Duff, KE; + view all (2016) Neuronal activity enhances tau propagation and tau pathology in vivo. Nature Neuroscience , 19 (8) pp. 1085-1092. 10.1038/nn.4328. Green open access

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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.

Type: Article
Title: Neuronal activity enhances tau propagation and tau pathology in vivo
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/nn.4328
Publisher version: http://dx.doi.org/10.1038/nn.4328
Language: English
Additional information: © 2016 Nature America, Inc. All rights reserved.
Keywords: Alzheimer's disease Diseases of the nervous system
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/1502403
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