Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons
Open accessAbstract
Many neurodegenerative diseases are characterized by the accumulation of insoluble protein aggregates, including neurofibrillary tangles comprised of tau in Alzheimer's disease and Lewy bodies composed of α-synuclein in Parkinson's disease. Moreover, different pathological proteins frequently codeposit in disease brains. To test whether aggregated α-synuclein can directly cross-seed tau fibrillization, we administered preformed α-synuclein fibrils assembled from recombinant protein to primary neurons and transgenic mice. Remarkably, we discovered two distinct strains of synthetic α-synuclein fibrils that demonstrated striking differences in the efficiency of cross-seeding tau aggregation, both in neuron cultures and in vivo. Proteinase K digestion revealed conformational differences between the two synthetic α-synuclein strains and also between sarkosyl-insoluble α-synuclein extracted from two subgroups of Parkinson's disease brains. We speculate that distinct strains of pathological α-synuclein likely exist in neurodegenerative disease brains and may underlie the tremendous heterogeneity of synucleinopathies.
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Evidence suggests that Aβ can directly affect α-synuclein toxicity, and tau protein and α-synuclein can directly interact promoting their co-assembly.
“Evidence suggests that Aβ can directly affect α-synuclein toxicity, and it is also known that tau protein and α-synuclein can directly interact promoting their co-assembly [124–126].”
From The neuropathological diagnosis of Alzheimer's disease (2019) · cites this paper as [126]
The Introduction reports that α-synuclein and tau synergistically promote each other’s fibrillization in vitro, and the paper investigates α-synuclein cross-seeding of tau aggregation. Our copy mentions Aβ plaques but does not say that Aβ directly affects α-synuclein toxicity. (LLM, conf=0.87)
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- Authors
- Guo, J. L., Covell, D. J., Daniels, J. P., Iba, M., Stieber, A., Zhang, B., Riddle, D. M., Kwong, L. K., Xu, Y., Trojanowski, J. Q., & Lee, V. M. Y.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Lee, Virginia M.Y.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 154
- Issue
- 1
- Pages
- 103-117
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3820001
- OpenAlex
- W1984766678
- Cited by
- 680
- References
- 11
- Citations by year
- 2026: 28 · 2025: 40 · 2024: 44 · 2023: 40 · 2022: 38 · 2021: 52 · 2020: 67 · 2019: 63 · 2018: 57 · 2017: 57 · 2016: 54 · 2015: 59 · 2014: 63 · 2013: 18
- FWCI
- 37.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P01AG017586, AG17586)
- National Institute of Neurological Disorders and Stroke (NS53488, P50NS053488)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- alpha-synuclein, tau protein, cross-seeding, protein aggregation, neurofibrillary tangles, Lewy bodies, Parkinson's disease, Alzheimer's disease, synucleinopathies, proteinase K resistance, primary neurons, transgenic mice
- MeSH terms
- Amyloid, Animals, Cells, Cultured, Embryo, Mammalian, Humans, Male, Mice, Transgenic, Neurons, Parkinson Disease, Recombinant Proteins, tau Proteins, Mice, alpha-Synuclein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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