Cited by 636Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

Tau oligomers impair memory and induce synaptic and mitochondrial dysfunction in wild-type mice

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Lasagna-Reeves, Cristian A, Castillo-Carranza, Diana L, Sengupta, Urmi, Clos, Audra L, Jackson, George R, Kayed, Rakez·2011·Molecular Neurodegeneration

Abstract

Background: The correlation between neurofibrillary tangles of tau and disease progression in the brains of Alzheimer's disease (AD) patients remains an area of contention. Innovative data are emerging from biochemical, cell-based and transgenic mouse studies that suggest that tau oligomers, a pre-filament form of tau, may be the most toxic and pathologically significant tau aggregate. Results: Here we report that oligomers of recombinant full-length human tau protein are neurotoxic in vivo after subcortical stereotaxic injection into mice. Tau oligomers impaired memory consolidation, whereas tau fibrils and monomers did not. Additionally, tau oligomers induced synaptic dysfunction by reducing the levels of synaptic vesicle-associated proteins synaptophysin and septin-11. Tau oligomers produced mitochondrial dysfunction by decreasing the levels of NADH-ubiquinone oxidoreductase (electron transport chain complex I), and activated caspase-9, which is related to the apoptotic mitochondrial pathway. Conclusions: This study identifies tau oligomers as an acutely toxic tau species in vivo, and suggests that tau oligomers induce neurodegeneration by affecting mitochondrial and synaptic function, both of which are early hallmarks in AD and other tauopathies. These results open new avenues for neuroprotective intervention strategies of tauopathies by targeting tau oligomers.

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Authors
Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Clos, A. L., Jackson, G. R., & Kayed, R.
Affiliations
The University of Texas Medical Branch at Galveston (US)
Corresponding author
Kayed, Rakez
Venue
Molecular Neurodegeneration
Published
2011-06-06
Volume
6
Issue
1
Pages
39-39
ISSN
1750-1326 (ISSN-L)
OpenAlex
W1968276382
Cited by
633
References
84
Citations by year
2026: 52 · 2025: 67 · 2024: 46 · 2023: 53 · 2022: 52 · 2021: 51 · 2020: 57 · 2019: 43 · 2018: 44 · 2017: 35 · 2016: 27 · 2015: 33 · 2014: 27 · 2013: 28 · 2012: 12
FWCI
15.93
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Molecular Neurodegeneration (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)
Funders
  • Alzheimer's Drug Discovery Foundation
  • Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch
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, neurotoxicity, memory consolidation, synaptic dysfunction, synaptophysin, mitochondrial dysfunction, complex I, caspase-9, apoptosis, neurofibrillary tangles, stereotactic injection, neurodegeneration

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