Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Tau in the brain interstitial fluid is fragmented and seeding-competent

Erica Barini, Gudrun Plotzky, Yulia Mordashova, Jonas Hoppe, Esther Rodriguez-Correa, Sonja Julier, Florie LePrieult, Ina Mairhofer, Mario Mezler, Sandra Biesinger, Miroslav Cik, Marcus W Meinhardt, Ebru Ercan-Herbst, Dagmar Ehrnhoefer, Andreas Striebinger, Karen Bodie, Corinna Klein, Laura Gasparini, Kerstin Schlegel
doi: https://doi.org/10.1101/2020.07.15.205724
Erica Barini
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gudrun Plotzky
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yulia Mordashova
3AbbVie Deutschland GmbH & Co. KG, Discovery and Exploratory Statistics (DIVES), AbbVie Deutschland GmbH & Co. KG, Knollstrasse, 67061, Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonas Hoppe
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Esther Rodriguez-Correa
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sonja Julier
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Florie LePrieult
2AbbVie Deutschland GmbH & Co. KG, Drug Metabolism and Pharmacokinetics, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ina Mairhofer
2AbbVie Deutschland GmbH & Co. KG, Drug Metabolism and Pharmacokinetics, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mario Mezler
2AbbVie Deutschland GmbH & Co. KG, Drug Metabolism and Pharmacokinetics, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sandra Biesinger
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miroslav Cik
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marcus W Meinhardt
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ebru Ercan-Herbst
4BioMed X GmbH Im Neuenheimer Feld 515 69120 Heidelberg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dagmar Ehrnhoefer
4BioMed X GmbH Im Neuenheimer Feld 515 69120 Heidelberg, Germany
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Striebinger
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Karen Bodie
5AbbVie Deutschland GmbH & Co. KG, Preclinical Safety, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Corinna Klein
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Gasparini
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kerstin.schlegel@abbvie.com
Kerstin Schlegel
1AbbVie Deutschland GmbH & Co. KG, Neuroscience Discovery, Knollstrasse, 67061 Ludwigshafen, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: kerstin.schlegel@abbvie.com
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

SUMMARY

In Alzheimer disease, Tau pathology is thought to propagate from cell to cell throughout interconnected brain areas. However, the forms of Tau released into the brain interstitial fluid (ISF) in vivo during the development of Tauopathy and their pathological relevance remain unclear. Combining in vivo microdialysis and biochemical analysis, we find that human Tau (hTau) present in brain ISF is truncated and comprises at least 10 distinct fragments spanning the entire Tau protein. The fragmentation pattern is similar across different Tau transgenic models, pathological stages and brain areas. ISF hTau concentration decreases during Tauopathy progression, while its phosphorylation increases. ISF from mice with established Tauopathy induces Tau aggregation in HEK293-Tau biosensor cells and notably, only a small fraction of Tau, separated by ultracentrifugation, is seeding competent. These results indicate that only a subset of Tau accounts for ISF seeding competence and have the potential to contribute to the propagation of Tau pathology.

Figure
  • Download figure
  • Open in new tab

Highlights

  • ✓ In transgenic mice, interstitial fluid comprises several Tau fragments spanning the entire Tau sequence.

  • ✓ Interstitial fluid Tau concentration decreases with Tauopathy progression, while phosphorylation increases.

  • ✓ Only interstitial fluid from mice with established Tauopathy is seeding competent in vitro.

  • ✓ Interstitial fluid seeding competence is driven by less soluble, aggregated and phosphorylated Tau species.

In Brief Barini et al. show that in the brain interstitial fluid of Tau transgenic mice, truncated Tau decreases, while its phosphorylation increases during the progression of pathology. A subset of less soluble, aggregated and phosphorylated ISF Tau induces Tau aggregation in cells.

Competing Interest Statement

The design, study conduct and financial support for this research were provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted July 17, 2020.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Tau in the brain interstitial fluid is fragmented and seeding-competent
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Tau in the brain interstitial fluid is fragmented and seeding-competent
Erica Barini, Gudrun Plotzky, Yulia Mordashova, Jonas Hoppe, Esther Rodriguez-Correa, Sonja Julier, Florie LePrieult, Ina Mairhofer, Mario Mezler, Sandra Biesinger, Miroslav Cik, Marcus W Meinhardt, Ebru Ercan-Herbst, Dagmar Ehrnhoefer, Andreas Striebinger, Karen Bodie, Corinna Klein, Laura Gasparini, Kerstin Schlegel
bioRxiv 2020.07.15.205724; doi: https://doi.org/10.1101/2020.07.15.205724
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Tau in the brain interstitial fluid is fragmented and seeding-competent
Erica Barini, Gudrun Plotzky, Yulia Mordashova, Jonas Hoppe, Esther Rodriguez-Correa, Sonja Julier, Florie LePrieult, Ina Mairhofer, Mario Mezler, Sandra Biesinger, Miroslav Cik, Marcus W Meinhardt, Ebru Ercan-Herbst, Dagmar Ehrnhoefer, Andreas Striebinger, Karen Bodie, Corinna Klein, Laura Gasparini, Kerstin Schlegel
bioRxiv 2020.07.15.205724; doi: https://doi.org/10.1101/2020.07.15.205724

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Neuroscience
Subject Areas
All Articles
  • Animal Behavior and Cognition (4855)
  • Biochemistry (10796)
  • Bioengineering (8045)
  • Bioinformatics (27307)
  • Biophysics (13987)
  • Cancer Biology (11127)
  • Cell Biology (16061)
  • Clinical Trials (138)
  • Developmental Biology (8788)
  • Ecology (13293)
  • Epidemiology (2067)
  • Evolutionary Biology (17364)
  • Genetics (11689)
  • Genomics (15924)
  • Immunology (11034)
  • Microbiology (26090)
  • Molecular Biology (10649)
  • Neuroscience (56564)
  • Paleontology (418)
  • Pathology (1732)
  • Pharmacology and Toxicology (3005)
  • Physiology (4547)
  • Plant Biology (9630)
  • Scientific Communication and Education (1615)
  • Synthetic Biology (2689)
  • Systems Biology (6978)
  • Zoology (1510)