α-Synuclein (α-syn) and tau aggregates are the neuropathological hallmarks of Parkinson’s disease (PD) and Alzheimer’s disease (AD), respectively, although both pathologies co-occur in patients with these diseases, suggesting possible crosstalk between them. To elucidate the interactions of pathological α-syn and tau, we sought to model these interactions. We show that increased accumulation of tau aggregates occur following simultaneous introduction of α-syn mousepreformed fibrils (mpffs) and AD lysate–derived tau seeds (AD-tau) both in vitro and in vivo. Interestingly, the absence of endogenous mouse α-syn in mice reduces the accumulation and spreading of tau, while the absence of tau did not affect the seeding or spreading capacity of α-syn. These in vivo results are consistent with our in vitro data wherein the presence of tau has no synergistic effects on α-syn. Our results point to the important role of α-syn as a modulator of tau pathology burden and spreading in the brains of AD, PDD, and DLB patients.
Skip Nav Destination
Close
Article navigation
4 January 2021
Article|
October 22 2020
α-Synuclein modulates tau spreading in mouse brains
In Special Collection:
Neurodegenerative Diseases: Biology & Therapeutics
Fares Bassil,
Fares Bassil
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
2
AbbVie, Foundational Neuroscience Center, Cambridge, MA
Search for other works by this author on:
Emily S. Meymand,
Emily S. Meymand
Data curation, Formal analysis, Investigation, Methodology, Resources, Validation, Visualization, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Hannah J. Brown,
Hannah J. Brown
Conceptualization, Data curation, Formal analysis
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Hong Xu,
Hong Xu
Investigation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Timothy O. Cox,
Timothy O. Cox
Formal analysis, Investigation, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Shankar Pattabhiraman,
Shankar Pattabhiraman
Formal analysis, Investigation, Validation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Chantal M. Maghames,
Chantal M. Maghames
Conceptualization, Methodology, Writing - review & editing
3
The Department of Cancer Biology and Abramson Family Cancer Research Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Qihui Wu,
Qihui Wu
Investigation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Bin Zhang,
Bin Zhang
Investigation, Methodology, Project administration, Resources, Supervision, Validation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
John Q. Trojanowski,
John Q. Trojanowski
Conceptualization, Formal analysis, Funding acquisition, Resources, Supervision, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Search for other works by this author on:
Virginia M.-Y. Lee
Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Writing - original draft, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Correspondence to Virginia M.-Y. Lee: vmylee@upenn.edu
Search for other works by this author on:
Fares Bassil
Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing - original draft, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
2
AbbVie, Foundational Neuroscience Center, Cambridge, MA
Emily S. Meymand
Data curation, Formal analysis, Investigation, Methodology, Resources, Validation, Visualization, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Hannah J. Brown
Conceptualization, Data curation, Formal analysis
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Hong Xu
Investigation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Timothy O. Cox
Formal analysis, Investigation, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Shankar Pattabhiraman
Formal analysis, Investigation, Validation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Chantal M. Maghames
Conceptualization, Methodology, Writing - review & editing
3
The Department of Cancer Biology and Abramson Family Cancer Research Institute, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Qihui Wu
Investigation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Bin Zhang
Investigation, Methodology, Project administration, Resources, Supervision, Validation
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
John Q. Trojanowski
Conceptualization, Formal analysis, Funding acquisition, Resources, Supervision, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Virginia M.-Y. Lee
Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Writing - original draft, Writing - review & editing
1
The Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA
Correspondence to Virginia M.-Y. Lee: vmylee@upenn.edu
Received:
November 20 2019
Revision Received:
March 12 2020
Accepted:
July 24 2020
Online Issn: 1540-9538
Print Issn: 0022-1007
Funding:
National Institute on Aging
(P30 AG010124, P01 AG17586, U19 AG062418)
National Institutes of Health
(NO AWARD)
© 2020 Bassil et al.
2020
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/).
J Exp Med (2021) 218 (1): e20192193.
Article history
Received:
November 20 2019
Revision Received:
March 12 2020
Accepted:
July 24 2020
Citation
Fares Bassil, Emily S. Meymand, Hannah J. Brown, Hong Xu, Timothy O. Cox, Shankar Pattabhiraman, Chantal M. Maghames, Qihui Wu, Bin Zhang, John Q. Trojanowski, Virginia M.-Y. Lee; α-Synuclein modulates tau spreading in mouse brains. J Exp Med 4 January 2021; 218 (1): e20192193. doi: https://doi.org/10.1084/jem.20192193
Download citation file:
Close
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Sign in via your Institution
Sign in via your Institution
1,209
Views
0
Citations
Suggested Content
Advertisement