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Cited by 90Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Trimeric Tau Is Toxic to Human Neuronal Cells at Low Nanomolar Concentrations

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Tian, Huilai, Davidowitz, Eliot, Lopez, Patricia, Emadi, Sharareh, Moe, James, Sierks, Michael·2013·International Journal of Cell Biology
DOI 10.1155/2013/260787PMC PMC3789488
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Abstract

In Alzheimer’s disease (AD), tau aggregates into fibrils and higher order neurofibrillary tangles, a key histopathological feature of AD. However, soluble oligomeric tau species may play a more critical role in AD progression since these tau species correlate better with neuronal loss and cognitive dysfunction. Recent studies show that extracellular oligomeric tau can inhibit memory formation and synaptic function and also transmit pathology to neighboring neurons. However, the specific forms of oligomeric tau involved in toxicity are still unknown. Here, we used two splice variants of recombinant human tau and generated monomeric, dimeric, and trimeric fractions of each isoform. The composition of each fraction was verified chromatographically and also by atomic force microscopy. The toxicity of each fraction toward both human neuroblastoma cells and cholinergic-like neurons was assessed. Trimeric, but not monomeric or dimeric, tau oligomers of both splice variants were neurotoxic at low nanomolar concentrations. Further characterization of tau oligomer species with disease-specific modifications and morphologies is necessary to identify the best targets for the development of biomarker and therapeutic development for AD and related tauopathies.

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  • Tau oligomers form prior to and independent of NFTs.

    “Several groups have demonstrated that tau oligomers, which form prior to and independent of NFTs, are the toxic agents responsible for synaptic dysfunction in AD and drive cognitive decline [26, 49, 50, 58, 95].”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [95]

    The Introduction (page unavailable) says oligomeric tau appears in early AD cytopathology and that synaptic dysfunction can occur before NFTs. It does not establish that tau oligomers themselves form before NFTs or that their formation is independent of NFTs. (LLM, conf=0.82)

    Experimental — accuracy not yet measured

  • Tau oligomers are the toxic agents responsible for synaptic dysfunction in AD and drive cognitive decline.

    “Several groups have demonstrated that tau oligomers, which form prior to and independent of NFTs, are the toxic agents responsible for synaptic dysfunction in AD and drive cognitive decline [26, 49, 50, 58, 95].”

    From Enhanced microglial dynamics and a paucity of tau seeding in the amyloid plaque microenvironment contribute to cognitive resilience in Alzheimer’s disease (2024) · cites this paper as [95]

    The Introduction reports that oligomeric tau induces synaptic dysfunction and that its levels correlate with memory loss in mice. It also describes oligomeric tau as implicated in AD progression, but does not establish that it is *the* agent responsible for synaptic dysfunction or that it drives cognitive decline in people with AD. The claim states those causal conclusions more firmly than the source does. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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References 59 · Cited by 90

Research works printed but not linked: 48

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Authors
Tian, H., Davidowitz, E., Lopez, P., Emadi, S., Moe, J., & Sierks, M.
Affiliations
  • Arizona State University (US)
  • Oligomerix, Inc., 3960 Broadway, New York, NY 10032, USA
Corresponding author
Sierks, Michael
ORCID
Venue
International Journal of Cell Biology
Publisher
Wiley
Published
2013
Volume
2013
Pages
1-9
ISSN
  • 1687-8876 (ISSN-L)
  • 1687-8884
DOI
10.1155/2013/260787
PMC
PMC3789488
OpenAlex
W2135785311
Cited by
90
References
59
Citations by year
2026: 1 · 2025: 4 · 2024: 11 · 2023: 6 · 2022: 7 · 2021: 15 · 2020: 9 · 2019: 9 · 2018: 3 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 4
FWCI
4.18
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Cell Biology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institute on Aging (AG029777)
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
neurotoxicity, Alzheimer's disease, tauopathy, neurofibrillary tangles, tau oligomers, neuroblastoma cells, cholinergic neurons, tau isoforms

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