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Cognitive defects are reversible in inducible mice expressing pro-aggregant full-length human Tau
Open accessAbstract
Neurofibrillary lesions of abnormal Tau are hallmarks of Alzheimer disease and frontotemporal dementias. Our regulatable (Tet-OFF) mouse models of tauopathy express variants of human full-length Tau in the forebrain (CaMKIIα promoter) either with mutation ΔK280 (pro-aggregant) or ΔK280/I277P/I308P (anti-aggregant). Co-expression of luciferase enables in vivo quantification of gene expression by bioluminescence imaging. Pro-aggregant mice develop synapse loss and Tau-pathology including missorting, phosphorylation and early pretangle formation, whereas anti-aggregant mice do not. We correlated hippocampal Tau pathology with learning/memory performance and synaptic plasticity. Pro-aggregant mice at 16 months of gene expression exhibited severe cognitive deficits in Morris water maze and in passive-avoidance paradigms, whereas anti-aggregant mice were comparable to controls. Cognitive impairment of pro-aggregant mice was accompanied by loss of hippocampal LTP in CA1 and CA3 areas and by a reduction of synaptic proteins and dendritic spines, although no neuronal loss was observed. Remarkably, memory and LTP recovered when pro-aggregant Tau was switched-OFF for ~4 months, Tau phosphorylation and missorting were reversed, and synapses recovered. Moreover, soluble and insoluble pro-aggregant hTau40 disappeared, while insoluble mouse Tau was still present. This study links early Tau pathology without neurofibrillary tangles and neuronal death to cognitive decline and synaptic dysfunction. It demonstrates that Tau-induced impairments are reversible after switching-OFF pro-aggregant Tau. Therefore, our mouse model may mimic an early phase of AD when the hippocampus does not yet suffer from irreversible cell death but cognitive deficits are already striking. It offers potential to evaluate drugs with regard to learning and memory performance.
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“Tau-mediated neurodegeneration arises from multiple pathological mechanisms, including loss of normal function [37–42], gain of toxic function [43–46], aggregation [44, 47–49], and mislocalization [50–52].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [43]
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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
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Lee, V. M.-Y., Goedert, M., & Trojanowski, J. Q. (2001) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.24.1.1121 · Cited by 2,480
Synapse 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
Tau-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
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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
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Qi, L., Fu, Z., Tu, M., Abdullah, R., Zhao, Y., Su, X., Zhou, D., & Peng, G. (2026) · The Journal of Prevention of Alzheimer s Disease · doi:10.1016/j.tjpad.2025.100473 · Cited by 8
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Polanco, J. C., & Götz, J. (2015) · The EMBO Journal · doi:10.15252/embj.201593311 · Cited by 8
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Vilaboa, N. E., & Voellmy, R. W. (2015) · CRC Press eBooks · doi:10.1201/b18002-29 · Cited by 5
Purification and Characterization of Low-n Tau Oligomers
Kaniyappan, S., Chandupatla, R., & Mandelkow�, E. (2018) · Methods in molecular biology · doi:10.1007/978-1-4939-7816-8_8 · Cited by 4
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Tsai, R. M., & Boxer, A. L. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9781316091586.021 · Cited by 1
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Chimal-Juárez, E., Patel, H., Jury-Garfe, N., Dabin, L. C., Vidal, R., Kim, J., & Lasagna-Reeves, C. A. (2026) · bioRxiv · doi:10.64898/2026.05.12.724684
Dickerson, B. C. (2015) · Cambridge University Press eBooks · doi:10.1017/cbo9781316091586.019
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Siahaan, A. M. P., Indharty, R. S., Chrestella, J., Sadewo, W., Tandean, S., & Syarifah, S. (2020) · Open Access Macedonian Journal of Medical Sciences · doi:10.3889/oamjms.2020.5471
Anglada‐Huguet, M., Endepols, H., Sydow, A., Hilgers, R., Neumaier, B., Drzezga, A. E., Kaniyappan, S., Mandelkow�, E., & Mandelkow, E. (2022) · Research Square · doi:10.21203/rs.3.rs-1363420/v1
Self-citationZampar, S. (2021) · eDiss (Georg-August-Universität Göttingen) · doi:10.53846/goediss-9004
Chung, D. C., Stankowski, J. N., & Petrucelli, L. (2017) · Oxford University Press eBooks · doi:10.1093/med/9780190681425.003.0056
Yang, Z., & Lei, P. (2024) · Scientia Sinica Vitae · doi:10.1360/ssv-2024-0201
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Vaz, M., Martins, T. S., Trigo, D., Silva, O. A. B. D. C. E., Amado, F. M. L., Vitorino, R. M. P., & Henriques, A. G. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05343-0 · Cited by 1
Additional file 1 of Synaptic tau: A pathological or physiological phenomenon?
Robbins, M., Clayton, E. L., & Schierle, G. S. K. (2021) · Figshare · doi:10.6084/m9.figshare.16599510
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Pires, G. (2021) · theses.fr (ABES) · doi:10.70675/45826fd6zd2c8z4b3dz91e0za5080544cb17
Astrocytes dysfunction in tauopathies
Augustin, E. (2023) · theses.fr (ABES) · doi:10.70675/a6b6a2f4zff42z4987z9ca0z62aca30c291c
Metadata
- Authors
- Van der Jeugd, A., Hochgräfe, K., Ahmed, T., Decker, J. M., Sydow, A., Hofmann, A., Wu, D., Messing, L., Balschun, D., D’Hooge, R., & Mandelkow, E.-M.
- Affiliations
- Center of Advanced European Studies and Research (DE)
- KU Leuven (BE)
- Max Planck Society (DE)
- Corresponding author
- Mandelkow, Eva-Maria
- Venue
- Acta Neuropathologica
- Published
- 2012-04-25
- Volume
- 123
- Issue
- 6
- Pages
- 787-805
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- PMC
- PMC4979687
- OpenAlex
- W2030674642
- Cited by
- 135
- References
- 83
- Citations by year
- 2026: 2 · 2025: 11 · 2024: 6 · 2023: 9 · 2022: 7 · 2021: 9 · 2020: 13 · 2019: 6 · 2018: 6 · 2017: 10 · 2016: 12 · 2015: 19 · 2014: 9 · 2013: 13 · 2012: 3
- FWCI
- 9.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- Max Planck Digital Library (submittedVersion)
- Lirias (submittedVersion)
- DZNE Pub (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Wellcome Trust (089703)
- Medical Research Council (MC_G1000734)
- 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
- tauopathy, Alzheimer's disease, frontotemporal dementia, cognitive impairment, hippocampal long-term potentiation, synaptic plasticity, synaptic loss, dendritic spines, tau phosphorylation, learning and memory, bioluminescence imaging
- MeSH terms
- Alzheimer Disease, Animals, Cognition Disorders, Disease Models, Animal, Hippocampus, Humans, Learning, Mice, Transgenic, Neuropsychological Tests, Synapses, Time Factors, Gene Expression, Neurofibrillary Tangles, tau Proteins, Long-Term Potentiation, Tauopathies, Mice
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