Tau Oligomers: Cytotoxicity, Propagation, and Mitochondrial Damage
Open accessAbstract
Aging has long been considered as the main risk factor for several neurodegenerative disorders including a large group of diseases known as tauopathies. Even though neurofibrillary tangles (NFTs) have been examined as the main histopathological hallmark, they do not seem to play a role as the toxic entities leading to disease. Recent studies suggest that an intermediate form of tau, prior to NFT formation, the tau oligomer, is the true toxic species. However, the mechanisms by which tau oligomers trigger neurodegeneration remain unknown. This review summarizes recent findings regarding the role of tau oligomers in disease, including release from cells, propagation from affected to unaffected brain regions, uptake into cells, and toxicity via mitochondrial dysfunction. A greater understanding of tauopathies may lead to future advancements in regards to prevention and treatment.
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Neurons can extracellularly release TauO, which serve as seeds that promote spreading and propagation of tau pathology in a prion-like fashion and induce cognitive deficits.
“Neurons can extracellularly release TauO, which serve as “seeds” that promote spreading and propagation of tau pathology in a prion‐like fashion and induce cognitive deficits. 11 , 12 , 13”
From Senescence, brain inflammation, and oligomeric tau drive cognitive decline in Alzheimer's disease: Evidence from clinical and preclinical studies (2024) · cites this paper as [13]
Current evidence suggests that small soluble tau species are more detrimental to cells than mature filaments.
“However, the mature filaments are unlikely to be the primary toxic species: current evidence suggests that small soluble species are more detrimental to cells (reviewed previously54,55).”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [54]
In cell models, soluble oligomeric tau can induce seeding of native tau, and small tau aggregates isolated from patients or animals with AD can induce tau pathology in mice.
“For example, in cell models, soluble oligomeric tau can induce seeding of native tau54,64, and small tau aggregates isolated from patients or animals with AD can induce tau pathology in mice54,64,65.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [54]
Tau oligomers promote toxicity in cell models to a greater extent than filamentous tau, and are linked to neurodegeneration and cognitive phenotypes in vivo.
“Tau oligomers promote toxicity in cell models to a greater extent than filamentous tau, and are linked to neurodegeneration and cognitive phenotypes in vivo54,55”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [54]
Oligomeric tau is the probable candidate for the most toxic species in tauopathies and is present in the brain at early stages of MCI and AD.
“Oligomeric tau has emerged as the probable candidate for the most toxic species in tauopathies, and is present in the brain at early stages of mild cognitive impairment (MCI) and AD54,55,61.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [54]
Tau-expressing cells secrete normal and pathological tau, which can be taken up by other cells and induce seeding of tau pathology.
“Tau-expressing cells secrete normal and pathological tau234, which can be taken up by other cells and induce seeding of tau pathology54,64,228.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [54]
In animal models that express tau only in certain brain regions, or that are injected with exogenous tau, spreading of tau pathology to anatomically connected regions occurs over time.
“In animal models that express tau only in certain brain regions, or that are injected with exogenous tau, spreading of tau pathology to anatomically connected regions occurs over time54,64,228.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [54]
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- Authors
- Shafiei, S. S., Guerrero-Muñoz, M. J., & Castillo-Carranza, D. L.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2017-04-04
- Volume
- 9
- Pages
- 83-83
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC5378766
- OpenAlex
- W2605143093
- Cited by
- 314
- References
- 95
- Citations by year
- 2026: 18 · 2025: 37 · 2024: 38 · 2023: 40 · 2022: 34 · 2021: 52 · 2020: 48 · 2019: 25 · 2018: 18 · 2017: 4
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Minority Health and Health Disparities (U54MD008621)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Keywords
- tau oligomers, tauopathy, neurodegeneration, mitochondrial dysfunction, neurofibrillary tangles, cytotoxicity, aging
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