The Role of Tau Oligomers in the Onset of Alzheimer's Disease Neuropathology
Abstract
Most neurodegenerative diseases are characterized by the presence of protein aggregates. Alzheimer's disease (AD) is the most common cause of dementia in people over age 60. One of the histopathological hallmarks of AD is the presence of tau protein aggregates. Historically, it has been thought that paired helical filaments (PHFs) were the toxic form of tau that assembled to form neurofibrillary tangles (NFTs), but recently there has been evidence that tau oligomers, which form before PHFs and NFTs, could be the structures mediating neurodegeneration even before the fibrillary tau is deposited. Here, we discuss the recent advances in tau oligomer research, their implications on AD and other tauopathies, the mechanisms of tau turnover by the principal protein clearance systems (the proteasome and autophagy), and the potential use of tau oligomers as drug targets for the development of new therapeutic approaches.
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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 [55]
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Tau-targeting therapies for Alzheimer disease
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Self-citationTau-targeting therapies for Alzheimer disease: Current status and future directions
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Role of tau protein in Alzheimer’s disease: The prime pathological player
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- Authors
- Cárdenas-Aguayo, M. D. C., Gómez-Virgilio, L., DeRosa, S., & Meraz-Ríos, M. A.
- Affiliations
- Molecular Biomedicine Department, CINVESTAV-IPN, Ave. Politécnico 2508, Colonia San Pedro Zacatenco, México City, D.F. 07360, México
- Nathan Kline Institute for Psychiatric Research (US)
- Venue
- ACS Chemical Neuroscience
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-10-15
- Volume
- 5
- Issue
- 12
- Pages
- 1178-1191
- ISSN
- 1948-7193 (ISSN-L)
- OpenAlex
- W2317252816
- Cited by
- 120
- References
- 148
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 13 · 2023: 9 · 2022: 15 · 2021: 9 · 2020: 12 · 2019: 12 · 2018: 10 · 2017: 6 · 2016: 12 · 2015: 3 · 2014: 1
- FWCI
- 0.86
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- ACS Chemical Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Consejo Nacional de Ciencia y Tecnología (203584)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- tau oligomers, Alzheimer's disease, tauopathy, neurofibrillary tangles, paired helical filaments, protein aggregation, neurodegeneration, proteasome, autophagy, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Brain, Humans, Models, Biological, tau Proteins
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