The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Tau Suppression in a Neurodegenerative Mouse Model Improves Memory Function
Open accessAbstract
Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.
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In the citing paper
“A mouse model of tauopathy (rTg4510) has been developed that specifically expresses tau in the forebrain but without amyloid plaques”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Santacruz et al., 2005
In the citing paper
“Behavioural and histological studies of the rTg4510 mouse have demonstrated cognitive deficits in learning and motor tasks and marked atrophy of brain regions known to be selectively vulnerable to AD such as the hippocampus and frontal cortex (Santacruz et al., 2005).”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Santacruz et al., 2005
In the citing paper
“The rTg4510 mouse mimics the features of clinical neurodegenerative diseases such as Alzheimer's disease with cognitive deficits, NFT formation and neuronal loss in the forebrain and hippocampus (Ramsden et al., 2005, Santacruz et al., 2005).”
From In vivo imaging of tau pathology using multi-parametric quantitative MRI (2015) · cites this paper as Santacruz et al., 2005
In the citing paper
“Mutant tau expression starts around postnatal day 7 and peaks at 1 month of age (34,35).”
In the citing paper
“From 2.5 months onward, phosphorylated tau protein and neuronal loss can be detected in the forebrain of these mice (14,34,35).”
In the citing paper
“In rTg4510 mice (34,35), tau with the mis-sense mutation P301L, found in some FTDP-17 cases (36), is over-expressed in the forebrain driven by the calcium-calmodulin kinase II (CaMKII) promoter.”
In the citing paper
“Substantial neurodegeneration is observed after 5 months of age, being most apparent in the hippocampal CA1 area (14,34,35).”
In the citing paper
“In rTg4510 mice (34,35), the age-dependent loss of neurons and progressive cognitive dysfunction closely mimic the clinical features of tauopathy.”
In the citing paper
“Given the evidence that soluble tau, rather than NFTs, is the pathologic tau species (Santacruz et al., 2005, Yoshiyama et al., 2007, Kopeikina et al., 2012, Lasagna-Reeves et al., 2012, Polydoro et al., 2014, Ghag et al., 2018)”
From Dendritic Spine Remodeling and Synaptic Tau Levels in PS19 Tauopathy Mice (2021) · cites this paper as Santacruz et al., 2005
In the citing paper
“suggesting that the neurodegeneration observed in these models reflects toxicity of soluble, non-aggregated forms of tau, and may recapitulate early stages of the abnormal metabolism and toxicity of tau [11–14].”
In the citing paper
“These findings indicate that soluble oligomeric tau may play a more essential role in neurodegeneration than insoluble fibrillar tau (including NFT), the “tau we can see”.”
From Tau and neuroinflammation in Alzheimer’s disease: interplay mechanisms and clinical translation (2023) · cites this paper as [26]
In the citing paper
“Intriguingly, suppression of the transgene at that point leads to a striking change in phenotype: The tangles remain unchanged in number (for at least 6 weeks), neuronal loss essentially ceases, and the cognitive performance of the animals improves remarkably.”
From All the Tau We Cannot See (2023) · cites this paper as [18]
In the citing paper
“In contrast, NFTs readily form in transgenic mice that express human tau containing mutations associated with FTLD; the most commonly used models being those that express 4R tau with P301L or P301S mutations[49, 91, 92, 135, 177].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [135]
Citations
Cites
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
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Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
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Self-citationA protein factor essential for microtubule assembly
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Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
Self-citationInclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death
Arrasate, M., Mitra, S., Schweitzer, E. S., Segal, M. R., & Finkbeiner, S. (2004) · Nature · doi:10.1038/nature02998 · Cited by 1,979
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611
Self-citationControl of memory formation through regulated expression of a CaMKII transgene
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., & Kandel, E. R. (1996) · Science · doi:10.1126/science.274.5293.1678 · Cited by 1,550
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526
Cited by
Sorted by citations
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359
Querfurth, H. W., & LaFerla, F. M. (2010) · New England Journal of Medicine · doi:10.1056/nejmra0909142 · Cited by 4,569
The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders
Zlokovic, B. V. (2008) · Neuron · doi:10.1016/j.neuron.2008.01.003 · Cited by 3,280
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
Self-citationRetractedThe molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Metadata
- Authors
- SantaCruz, K., Lewis, J., Spires, T., Paulson, J., Kotilinek, L., Ingelsson, M., Guimaraes, A., DeTure, M., Ramsden, M., McGowan, E., Forster, C., Yue, M., Orne, J., Janus, C., Mariash, A., Kuskowski, M., Hyman, B., Hutton, M., & Ashe, K. H.
- Affiliations
- University of Minnesota (US)
- Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
- Corresponding author
- SantaCruz, K.
- Lewis, J.
- Ashe, K. H.
- ORCID
- Venue
- Science
- Published
- 2005-07-15
- Volume
- 309
- Issue
- 5733
- Pages
- 476-481
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC1574647
- OpenAlex
- W2135309154
- Semantic Scholar
- 213e98528b0a0d2c141035b1b70266409044bd37
- Cited by
- 2,014
- References
- 26
- Citations by year
- 2026: 45 · 2025: 71 · 2024: 93 · 2023: 104 · 2022: 96 · 2021: 99 · 2020: 141 · 2019: 92 · 2018: 109 · 2017: 115 · 2016: 85 · 2015: 103 · 2014: 109 · 2013: 96 · 2012: 107
- FWCI
- 51.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- National Institutes of Health (5r01ns046355-03)
- U.S. Public Health Service (R01-026252)
- National Institute on Aging (R01AG026249, R01AG008487, P01AG015453, R01AG026252, T31-AG00277, P50AG005134)
- National Institute of Neurological Disorders and Stroke (R01NS082672, R01-NS046355, R01-NS46355, R01NS033249)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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 protein, neurofibrillary tangles, tauopathy, memory impairment, cognitive decline, neuronal loss, transgenic mouse model, age-related neurodegeneration
- MeSH terms
- Aging, Animals, Atrophy, Brain, Cognition, Doxycycline, Hippocampus, Humans, Memory, Mice, Transgenic, Neuronal Plasticity, Neurons, Organ Size, Phosphorylation, RNA, Messenger, Solubility, Neurofibrillary Tangles, tau Proteins, Disease Progression, Maze Learning, Neurodegenerative Diseases, Mice
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