Tau Oligomers as Potential Targets for Immunotherapy for Alzheimers Disease and Tauopathies
Abstract
The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer disease (AD) and many neurodegenerative diseases. For a long time research has focused on neurofibrillary tangles (NFTs) and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. The correlation between these structures and disease progression produced conflicting results; moreover, the mechanism of their formation remains poorly understood. Lately, the significance and toxicity of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of Aβ toxicity in AD; specifically, aggregates of a size intermediate between monomers and NFTs the so-called tau oligomers. Tremendous efforts have been devoted toward the optimization of a safe vaccine for AD by targeting Aβ peptide; despite the disappointing results, these studies produced a wealth of useful knowledge, which should be considered in developing tau-based immunotherapy. Herein, we discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.
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Smaller, soluble tau oligomers (TauO), not neurofibrillary tangles (NFTs), are the most toxic tau species.
“our laboratory and others found that smaller, soluble tau oligomers (TauO) —not NFTs—are the most toxic tau species. 9 , 10 , 11”
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 [9]
Elevated levels of TauO are present in the brain, cerebrospinal fluid, and sera from Alzheimer's disease patients with clinical severity.
“we observed elevated levels of TauO in the brain, cerebrospinal fluid (CSF), and sera from AD patients with clinical severity, 9 , 15 , 16 , 17 , 18 , 19 , 20”
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 [9]
TauO, senescence, and inflammaging are crucial elements in Alzheimer's disease and may cooperatively trigger complex pathomechanisms involved in Alzheimer's disease progression and cognitive decline.
“These findings suggest that TauO, senescence, and inflammaging are crucial elements in AD and may cooperatively trigger the underlying complex pathomechanisms involved in AD progression and cognitive decline. 9 , 29 , 30 , 31 , 32 , 33”
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 [9]
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- Authors
- A. Lasagna-Reeves, C., L. Castillo-Carranza, D., R. Jackson, G., & Kayed, R.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- ORCID
- Kayed, R.
- Venue
- Current Alzheimer Research
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2011-09-01
- Volume
- 8
- Issue
- 6
- Pages
- 659-665
- ISSN
- 1567-2050 (ISSN-L)
- OpenAlex
- W2140050496
- Cited by
- 80
- References
- 0
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 2 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 3 · 2018: 7 · 2017: 11 · 2016: 3 · 2015: 8 · 2014: 7 · 2013: 9 · 2012: 5
- FWCI
- 5.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Alzheimer Research (publishedVersion)
- PubMed (publishedVersion)
- 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, tauopathy, Alzheimer's disease, immunotherapy, tau aggregation, neurofibrillary tangles, amyloid-beta toxicity, hyperphosphorylated tau, neurodegeneration
- MeSH terms
- Alzheimer Disease, Humans, Immunotherapy, tau Proteins, Tauopathies
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