α-Synuclein Oligomers Induce a Unique Toxic Tau Strain

D.L. Castillo-Carranza, M.J. Guerrero-Muñoz, U. Sengupta, J.E. Gerson, R. Kayed

Research output: Contribution to journalArticlepeer-review

61 Citations (Scopus)

Abstract

Background: The coexistence of α-synuclein and tau aggregates in several neurodegenerative disorders, including Parkinson's disease and Alzheimer's disease, raises the possibility that a seeding mechanism is involved in disease progression. Methods: To further investigate the role of α-synuclein in the tau aggregation pathway, we performed a set of experiments using both recombinant and brain-derived tau and α-synuclein oligomers to seed monomeric tau aggregation in vitro and in vivo. Brain-derived tau oligomers were isolated from well-characterized cases of progressive supranuclear palsy (n = 4) and complexes of brain-derived α-synuclein/tau oligomers isolated from patients with Parkinson's disease (n = 4). The isolated structures were purified and characterized by standard biochemical methods, then injected into Htau mice (n = 24) to assess their toxicity and role in tau aggregation. Results: We found that α-synuclein induced a distinct toxic tau oligomeric strain that avoids fibril formation. In vivo, Parkinson's disease brain–derived α-synuclein/tau oligomers administered into Htau mouse brains accelerated endogenous tau oligomer formation concurrent with increasing cell loss. Conclusions: Our findings provide evidence, for the first time, that α-synuclein enhances the harmful effects of tau, thus contributing to disease progression.

Original languageEnglish
Pages (from-to)499-508
Number of pages10
JournalBiological Psychiatry
Volume84
Issue number7
DOIs
Publication statusPublished - 1 Oct 2018
Externally publishedYes

Bibliographical note

Copyright © 2018 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry

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