Neuronal Activity Enhances Tau Propagation and Tau Pathology in Vivo

Overview

Journal Nat Neurosci

Date 2016 Jun 21

PMID 27322420

Citations 420

Authors

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

Affiliations

Soon will be listed here.

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.

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