The DOI matches its Crossref record; 75 of the 76 references it cites were found in a registry or an index.
Passive Immunization with Tau Oligomer Monoclonal Antibody Reverses Tauopathy Phenotypes without Affecting Hyperphosphorylated Neurofibrillary Tangles
Open accessAbstract
Recent findings suggest that tau oligomers, which form before neurofibrillary tangles (NFTs), are the true neurotoxic tau entities in neurodegenerative tauopathies, including Alzheimer's disease (AD). Studies in animal models of tauopathy suggest that tau oligomers play a key role in eliciting behavioral and cognitive impairments. Here, we used a novel tau oligomer-specific monoclonal antibody (TOMA) for passive immunization in mice expressing mutant human tau. A single dose of TOMA administered either intravenously or intracerebroventricularly was sufficient to reverse both locomotor and memory deficits in a mouse model of tauopathy for 60 d, coincident with rapid reduction of tau oligomers but not phosphorylated NFTs or monomeric tau. Our data demonstrate that antibody protection is mediated by extracellular and rapid peripheral clearance. These findings provide the first direct evidence in support of a critical role for tau oligomers in disease progression and validate tau oligomers as a target for the treatment of AD and other neurodegenerative tauopathies.
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In the citing paper
“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 [16]
In the citing paper
“significant advancements have been made in the development of novel anti‐tau antibodies that specifically recognize disease‐relevant tau strains and conformations.”
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 [16]
In the citing paper
“These antibodies target unique conformational epitopes, independent of specific linear amino acid sequences, and exhibit preferences for different subsets of tau oligomers.”
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 [16]
In the citing paper
“In addition, monoclonal antibodies against the amino-terminal or repeat domain (306–320) region209–215, oligomeric tau216,217, misfolded tau201,218,219, pSer202220,221, pThr231208 pSer409222, pSer413223 and pSer422224 have proved to be efficacious in tauopathy models.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [216]
In the citing paper
“Indeed, several reports are available of antibodies that are capable of reducing tau levels and preventing spreading without apparently entering neurons216,218,239.”
From Tau-targeting therapies for Alzheimer disease (2018) · cites this paper as [216]
Citations
Cites
1 retracted
Masliah, E., Rockenstein, E. M., Mante, M., Crews, L. A., Spencer, B. J., Adame, A., Patrick, C., Trejo, M., Ubhi, K. K., Rohn, T. T., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019338 · Cited by 422 · cited 5×
“…exclusive and it has been demonstrated that different clearance mechanisms can be activated to different degrees depending on the antibody and its target (DeMattos et al., 2001; Levites et al., 2006; Sigurdsson, 2008; Golde et al., 2009; Masliah et al., 2011; Morgan, 2011; Ubhi and Masliah, 2011).”
BackgroundInfluentialRetractedSynapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · cited 1×
“…metastable tau aggregates such as NFTs are not causally linked to tauopathy phenotypes in animal models (Wittmann et al., 2001; Santacruz et al., 2005; Berger et al., 2007; Yoshiyama et al., 2007; Polydoro et al., 2009; LasagnaReeves et al., 2011b; Spires-Jones et al., 2011; Cowan et al., 2012).”
BackgroundTau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174 · cited 3×
“In addition, tau mutations can cause disorders such as familial frontotemporal dementia (for review, see Ballatore et al., 2007).”
BackgroundInfluentialTau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., et al. (2005) · Science · doi:10.1126/science.1113694 · Cited by 2,014
Bard, F., Cannon, C., Barbour, R., Burke, R.-L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., et al. (2000) · Nature Medicine · doi:10.1038/78682 · Cited by 2,012
Reducing Endogenous Tau Ameliorates Amyloid ß-Induced Deficits in an Alzheimer's Disease Mouse Model
Roberson, E. D., Scearce-Levie, K., Palop, J. J., Yan, F., Cheng, I. H., Wu, T., Gerstein, H., Yu, G.-Q., & Mucke, L. (2007) · Science · doi:10.1126/science.1141736 · Cited by 1,892
Neuronal loss correlates with but exceeds neurofibrillary tangles in Alzheimer's disease
Gómez‐Isla, T., Hollister, R., West, H., Mui, S., Growdon, J. H., Petersen, R. C., Parisi, J. E., & Hyman, B. T. (1997) · Annals of Neurology · doi:10.1002/ana.410410106 · Cited by 1,489 · cited 1×
“…human AD brain, NFT-containing neurons can survive for decades (Morsch et al., 1999) and neuronal loss precedes or is independent of NFT formation (Gómez-Isla et al., 1997; Terry, 2000; Maeda et al., 2006; van de Nes et al., 2008), suggesting that other tau species may contribute to earlier…”
BackgroundLewis, J., McGowan, E., Rockwood, J., Melrose, H., Nacharaju, P., Van Slegtenhorst, M., Gwinn-Hardy, K., Murphy, M. P., Baker, M., Yu, X., et al. (2000) · Nature Genetics · doi:10.1038/78078 · Cited by 1,371 · cited 3×
“The JNPL3 mouse model (Lewis et al., 2000) expresses a frontotemporal dementia-associated human mutant tau transgene (P301L) and has been used previously for tau immunotherapy (Asuni et al., 2007; Chai et al., 2011; Bi et al., 2011).”
MethodDeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J.-C., Paul, S. M., & Holtzman, D. M. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.151261398 · Cited by 1,298
Augustinack, J. C., Schneider, A., Mandelkow, E.-M., & Hyman, B. T. (2002) · Acta Neuropathologica · doi:10.1007/s004010100423 · Cited by 998
Cited by
Sorted by citations
Tau in physiology and pathology
Wang, Y., & Mandelkow, E. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2015.1 · Cited by 2,251
Clearance systems in the brain—implications for Alzheimer disease
Tarasoff-Conway, J. M., Carare, R. O., Osorio, R. S., Glodzik, L., Butler, T., Fieremans, E., Axel, L., Rusinek, H., Nicholson, C., Zlokovic, B. V., et al. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.119 · Cited by 1,678
Depletion of microglia and inhibition of exosome synthesis halt tau propagation
Asai, H., Ikezu, S., Tsunoda, S., Medalla, M., Luebke, J., Haydar, T., Wolozin, B., Butovsky, O., Kügler, S., & Ikezu, T. (2015) · Nature Neuroscience · doi:10.1038/nn.4132 · Cited by 1,591
Tau-targeting therapies for Alzheimer disease
Congdon, E. E., & Sigurdsson, E. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0013-z · Cited by 1,113
Tau and neurodegenerative disease: the story so far
Iqbal, K., Liu, F., & Gong, C.-X. (2016) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.225 · Cited by 806
Metadata
- Authors
- Castillo-Carranza, D. L., Sengupta, U., Guerrero-Muñoz, M. J., Lasagna-Reeves, C. A., Gerson, J. E., Singh, G., Estes, D. M., Barrett, A. D. T., Dineley, K. T., Jackson, G. R., & Kayed, R.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- ORCID
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2014-03-19
- Volume
- 34
- Issue
- 12
- Pages
- 4260-4272
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6608097
- OpenAlex
- W1990986671
- Cited by
- 278
- References
- 76
- Citations by year
- 2026: 8 · 2025: 13 · 2024: 15 · 2023: 21 · 2022: 13 · 2021: 20 · 2020: 30 · 2019: 25 · 2018: 34 · 2017: 27 · 2016: 21 · 2015: 28 · 2014: 23
- FWCI
- 21.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Drug Discovery Foundation
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau oligomers, passive immunization, monoclonal antibodies, TOMAS, tauopathy, Alzheimer's disease, neurofibrillary tangles, hyperphosphorylated tau, locomotor deficits, memory impairment, antibody clearance, neurodegenerative disease treatment
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Immunization, Passive, Phosphorylation, Neurofibrillary Tangles, tau Proteins, Disease Progression, Tauopathies, Mice
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