Journal
BIOLOGICAL PSYCHIATRY
Volume 84, Issue 7, Pages 499-508Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2017.12.018
Keywords
Alpha-synuclein; Oligomeric complexes; Seeding; Strain; Tau oligomers; Toxicity
Categories
Funding
- Michael J. Fox Foundation
- Cullen Trust
- Mitchell Center for Neurodegenerative Diseases
- Sealy Center for Vaccine Development
- National Institutes of Health [AG054025, RFA1AG055771, NS094557]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS094557] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [RF1AG055771, R01AG054025] Funding Source: NIH RePORTER
Ask authors/readers for more resources
BACKGROUND: The coexistence of alpha-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 alpha-synuclein in the tau aggregation pathway, we performed a set of experiments using both recombinant and brain-derived tau and alpha-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 alpha-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 alpha-synuclein induced a distinct toxic tau oligomeric strain that avoids fibril formation. In vivo, Parkinson's disease brain-derived alpha-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 alpha-synuclein enhances the harmful effects of tau, thus contributing to disease progression.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available