Tau oligomers mediate α-synuclein toxicity and can be targeted by immunotherapy

J.E. Gerson, K.M. Farmer, N. Henson, D.L. Castillo-Carranza, M. Carretero Murillo, U. Sengupta, A. Barrett, R. Kayed

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57 Citations (Scopus)


Background: We have evaluated the efficacy of targeting the toxic, oligomeric form of tau protein by passive immunotherapy in a mouse model of synucleinopathy. Parkinson's disease and Lewy body dementia are two of the most common neurodegenerative disorders and are primarily characterized by the accumulation of α-synuclein in Lewy bodies. However, evidence shows that smaller, oligomeric aggregates are likely the most toxic form of the protein. Moreover, a large body of research suggests that α-synuclein interacts with tau in disease and may act in a synergistic mechanism, implicating tau oligomers as a potential therapeutic target. Methods: We treated seven-month-old mice overexpressing mutated α-synuclein (A53T mice) with tau oligomer-specific monoclonal antibody (TOMA) and a control antibody and assessed both behavioral and pathological phenotypes. Results: We found that A53T mice treated with TOMA were protected from cognitive and motor deficits two weeks after a single injection. Levels of toxic tau oligomers were specifically decreased in the brains of TOMA-treated mice. Tau oligomer depletion also protected against dopamine and synaptic protein loss. Conclusion: These results indicate that targeting tau oligomers is beneficial for a mouse model of synucleinopathy and may be a viable therapeutic strategy for treating diseases in which tau and α-synuclein have a synergistic toxicity.

Original languageEnglish
Pages (from-to)13
JournalMolecular Neurodegeneration
Issue number1
Publication statusPublished - 15 Mar 2018
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by the Michael J. Fox Foundation, the Mitchell Center for Neurodegenerative Disease, the Gilson Longerbaugh foundation, the Sealy Center for Vaccine Development and NIH grants R01AG054025, R01NS094557 and R01AG055771 (R.K).

Publisher Copyright:
© 2018 The Author(s).

Copyright 2018 Elsevier B.V., All rights reserved.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


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