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Nat Neurosci. 2016 Aug;19(8):1085-92. doi: 10.1038/nn.4328. Epub 2016 Jun 20.

Neuronal activity enhances tau propagation and tau pathology in vivo.

Author information

1
Taub Institute, Columbia University Medical Center, New York, New York, USA.
2
Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York, USA.
3
Department of Neurology, Columbia University Medical Center, New York, New York, USA.
4
Center for Alzheimer's and Neurodegenerative Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
5
Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
6
Department of Molecular Neuroscience, Institute of Neurology, University College, London, UK.
7
Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, New York, USA.

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.

PMID:
27322420
PMCID:
PMC4961585
DOI:
10.1038/nn.4328
[Indexed for MEDLINE]
Free PMC Article

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