Phosphorylation of Tau at S422 is enhanced by Aβ in TauPS2APP triple transgenic mice
Open accessAbstract
Amyloid beta peptides and microtubule-associated protein Tau are misfolded and form aggregates in brains of Alzheimer's disease patients. To examine their specific roles in the pathogenesis of Alzheimer's disease and their relevance in neurodegenerative processes, we have created TauPS2APP triple transgenic mice that express human mutated Amyloid Precursor Protein, presenilin 2 and Tau. We present a cross-sectional analysis of these mice at 4, 8, 12 and 16 months of age. By comparing with single transgenic Tau mice, we demonstrate that accumulation of Abeta in TauPS2APP triple transgenic mice impacts on Tau pathology by increasing the phosphorylation of Tau at serine 422, as determined by a novel immunodetection method that is able to reliably measure phospho-Tau species in transgenic mouse brains. The TauPS2APP triple transgenic mouse model will be very useful for studying the effect of new therapeutic paradigms on amyloid deposition and downstream neurofibrillary tangle development.
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Findings in models harboring transgenic Aβ peptides in the absence of APP overexpression strikingly contrast the obvious exacerbation of tau pathology observed in tau transgenic mice when crossed with mouse models of AD overexpressing mutant APP.
“These findings in models harboring transgenic Aβ peptides in the absence of APP overexpression strikingly contrast the obvious exacerbation of tau pathology observed in tau transgenic mice when crossed with mouse models of AD overexpressing mutant APP [7,8,9,10,11,12,13,36].”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [7]
A limited number of studies have reported animal models that display both plaques and tangles.
“A limited number of studies have reported the development of animal models that display both plaques and tangles [10, 51, 91, 109, 121].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [51]
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- Authors
- Grueninger, F., Bohrmann, B., Czech, C., Ballard, T. M., Frey, J. R., Weidensteiner, C., von Kienlin, M., & Ozmen, L.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- University Medical Center Freiburg (DE)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 37
- Issue
- 2
- Pages
- 294-306
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2020300726
- Cited by
- 117
- References
- 65
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 16 · 2019: 8 · 2018: 3 · 2017: 6 · 2016: 8 · 2015: 4 · 2014: 6 · 2013: 7 · 2012: 7
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- 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 phosphorylation, amyloid-beta, Alzheimer's disease, presenilin 2, amyloid precursor protein, neurofibrillary tangles, tau pathology, amyloid deposition
- MeSH terms
- Alzheimer Disease, Animals, Brain, Cross-Sectional Studies, Disease Models, Animal, Gene Expression Regulation, Genetic Markers, Humans, Immunohistochemistry, Mice, Transgenic, Phosphorylation, Biomarkers, Up-Regulation, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Genetic Predisposition to Disease, Mice, Presenilin-2, Plaque, Amyloid
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