Skip to main content

Main menu

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Archive
    • Subject Collections
    • Special Collections
  • Reviews & Opinions
    • Editorials
    • Found in Translation
    • Insights
    • People & Ideas
    • Perspectives
    • Reviews
    • Viewpoints
  • Alerts
  • About
    • History
    • Editors & Staff
    • Policies & Permissions
    • Advertise
    • Contact Us
    • Privacy Policy
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Publication Fees
    • Author Services
  • Subscriptions
  • Rockefeller University Press
  • JCB
  • JEM
  • JGP
  • LSA

User menu

  • Log in

Search

  • Advanced search
JEM
  • Rockefeller University Press
  • JCB
  • JEM
  • JGP
  • LSA
  • Log in
JEM

Advanced Search

  • Home
  • Articles
    • Newest Articles
    • Current Issue
    • Archive
    • Subject Collections
    • Special Collections
  • Reviews & Opinions
    • Editorials
    • Found in Translation
    • Insights
    • People & Ideas
    • Perspectives
    • Reviews
    • Viewpoints
  • Alerts
  • About
    • History
    • Editors & Staff
    • Policies & Permissions
    • Advertise
    • Contact Us
    • Privacy Policy
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Publication Fees
    • Author Services
  • Subscriptions

You are here

jem Home » 2018 Archive » 3 September » 215 (9): 2355
Article

TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading

Heidi Martini-Stoica, Allysa L. Cole, Daniel B. Swartzlander, Fading Chen, Ying-Wooi Wan, Lakshya Bajaj, David A. Bader, View ORCID ProfileVirginia M.Y. Lee, John Q. Trojanowski, Zhandong Liu, View ORCID ProfileMarco Sardiello, View ORCID ProfileHui Zheng  Correspondence email
Heidi Martini-Stoica
Huffington Center on Aging, Baylor College of Medicine, Houston, TXInterdepartmental Program of Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TXMedical Scientist Training Program, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allysa L. Cole
Huffington Center on Aging, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Daniel B. Swartzlander
Huffington Center on Aging, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fading Chen
Huffington Center on Aging, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ying-Wooi Wan
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TXDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lakshya Bajaj
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TXDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David A. Bader
Medical Scientist Training Program, Baylor College of Medicine, Houston, TXDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Virginia M.Y. Lee
Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Virginia M.Y. Lee
John Q. Trojanowski
Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, PA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Zhandong Liu
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TXDepartment of Pediatrics, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marco Sardiello
Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TXDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marco Sardiello
Hui Zheng
Huffington Center on Aging, Baylor College of Medicine, Houston, TXInterdepartmental Program of Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TXDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Hui Zheng
  • For correspondence: huiz@bcm.edu
DOI: 10.1084/jem.20172158 | Published August 14, 2018
  • Article
  • Figures & Data
  • Info
  • Metrics
  • Preview PDF
Loading

Abstract

The progression of tau pathology in Alzheimer’s disease follows a stereotyped pattern, and recent evidence suggests a role of synaptic connections in this process. Astrocytes are well positioned at the neuronal synapse to capture and degrade extracellular tau as it transits the synapse and hence could potentially have the ability to inhibit tau spreading and delay disease progression. Our study shows increased expression and activity of Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, in response to tau pathology in both human brains with dementia and transgenic mouse models. Exogenous TFEB expression in primary astrocytes enhances tau fibril uptake and lysosomal activity, while TFEB knockout has the reverse effect. In vivo, induced TFEB expression in astrocytes reduces pathology in the hippocampus of PS19 tauopathy mice, as well as prominently attenuates tau spreading from the ipsilateral to the contralateral hippocampus in a mouse model of tau spreading. Our study suggests that astrocytic TFEB plays a functional role in modulating extracellular tau and the propagation of neuronal tau pathology in tauopathies such as Alzheimer’s disease.

  • Submitted: 27 November 2017
  • Revision received 11 May 2018
  • Accepted: 20 July 2018
Creative Commons logoCreative Commons logohttp://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

View Full Text
© 2018 Martini-Stoica et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.

Pay Per Article - You may access this article (from the computer you are currently using) for 2 days for US$30.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

Activate

ACTIVATE Your Individual Subscription 

ACTIVATE Your Institutional Subscription

Subscribe/Renew

Subscribe or Renew here.

Previous articleNext article
Back to top
Citation Tools
TFEB enhances astroglial uptake of extracellular tau species and reduces tau spreading
Heidi Martini-Stoica, Allysa L. Cole, Daniel B. Swartzlander, Fading Chen, Ying-Wooi Wan, Lakshya Bajaj, David A. Bader, Virginia M.Y. Lee, John Q. Trojanowski, Zhandong Liu, Marco Sardiello, Hui Zheng
Journal of Experimental Medicine Sep 2018, 215 (9) 2355-2377; DOI: 10.1084/jem.20172158

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Alerts
Sign In to Email Alerts with your Email Address

Email logo Twitter logo Facebook logo Mendeley logo Reddit logo CiteULike logo LinkedIn logo
The Journal of Experimental Medicine: 216 (2)

Current Issue

February 4, 2019
Volume 216, No. 2

  • Table of Contents
  • All Issues

Jump To

  • Article
    • Abstract
    • Introduction
    • Results
    • Discussion
    • Materials and methods
    • Acknowledgments
    • References
  • Figures & Data
  • Info
  • Metrics
  • Preview PDF
 

Subjects

  • Neuroscience

ARTICLES

  • Current Issue
  • Newest Articles
  • Archive
  • Alerts
  • RSS feeds

FOR AUTHORS

  • Submit a Manuscript
  • Instructions for Authors

ABOUT

  • About JEM
  • Editors & Staff
  • Policies & Permissions
  • Advertise
  • Contact Us
  • Feedback
  • Newsroom
  • Privacy Policy

CONNECT WITH JEM

  • Email
  • Facebook
  • Twitter
  • RSS
  • Instagram

Online ISSN: 1540-9538
Print ISSN: 0022-1007

Copyright © 2019 JEM by Rockefeller University Press