α-Synuclein Oligomers Induce a Unique Toxic Tau Strain

Diana L. Castillo-Carranza, Marcos J. Guerrero-Muñoz, Urmi Sengupta, Julia E. Gerson, Rakez Kayed

Research output: Contribution to journalArticle

9 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 (US)
JournalBiological Psychiatry
DOIs
StateAccepted/In press - Jan 1 2018

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Synucleins
Poisons
Parkinson Disease
Brain
Disease Progression
Progressive Supranuclear Palsy
Neurodegenerative Diseases
Seeds
Alzheimer Disease

Keywords

  • Alpha-synuclein
  • Oligomeric complexes
  • Seeding
  • Strain
  • Tau oligomers
  • Toxicity

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Castillo-Carranza, D. L., Guerrero-Muñoz, M. J., Sengupta, U., Gerson, J. E., & Kayed, R. (Accepted/In press). α-Synuclein Oligomers Induce a Unique Toxic Tau Strain. Biological Psychiatry. https://doi.org/10.1016/j.biopsych.2017.12.018

α-Synuclein Oligomers Induce a Unique Toxic Tau Strain. / Castillo-Carranza, Diana L.; Guerrero-Muñoz, Marcos J.; Sengupta, Urmi; Gerson, Julia E.; Kayed, Rakez.

In: Biological Psychiatry, 01.01.2018.

Research output: Contribution to journalArticle

Castillo-Carranza, Diana L. ; Guerrero-Muñoz, Marcos J. ; Sengupta, Urmi ; Gerson, Julia E. ; Kayed, Rakez. / α-Synuclein Oligomers Induce a Unique Toxic Tau Strain. In: Biological Psychiatry. 2018.
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