Accelerated amyloid deposition, neurofibrillary degeneration and neuronal loss in double mutant APP/tau transgenic mice
Open accessAbstract
Even though the idea that amyloid beta peptide accumulation is the primary event in the pathogenesis of Alzheimer's disease has become the leading hypothesis, the causal link between aberrant amyloid precursor protein processing and tau alterations in this type of dementia remains controversial. We further investigated the role of beta-amyloid production/deposition in tau pathology and neuronal cell death in the mouse brain by crossing Tg2576 and VLW lines expressing human mutant amyloid precursor protein and human mutant tau, respectively. The resulting double transgenic mice showed enhanced amyloid deposition accompanied by neurofibrillary degeneration and overt neuronal loss in selectively vulnerable brain limbic areas. These findings challenge the idea that tau pathology in Alzheimer's disease is merely a downstream effect of amyloid production/deposition and suggest that reciprocal interactions between beta-amyloid and tau alterations may take place in vivo.
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In APP/Tau mice (Tg2576 crossed to VLW lines), stereology-based neuron counts revealed significantly reduced neuron numbers in the CA1 and entorhinal cortex.
“While neither neurofibrillary tangle formation nor significant neuron loss in CA1 has been reported in the single-transgenic Tg2576 model [66], stereology-based neuron counts revealed significantly reduced neuron numbers in the CA1 and entorhinal cortex in APP/Tau mice [55].”
From Neuron Loss in Alzheimer’s Disease: Translation in Transgenic Mouse Models (2020) · cites this paper as [55]
One initial study suggested that MAPT pathology increases Aβ pathology.
“with only one initial study suggesting that MAPT pathology increases Aβ pathology (Ribe et al., 2005).”
From β-amyloid accumulation enhances microtubule associated protein tau pathology in an APPNL-G-F/MAPTP301S mouse model of Alzheimer’s disease (2024) · cites this paper as Ribe et al., 2005
An up to 5-fold increased amyloid load was observed in 16-month-old Tg2576 mice that had been crossed with a tau transgenic line harboring a triple-mutant tau (G272V, P310L, R406W).
“However, it has to be noted that an up to 5-fold increased amyloid load was observed in 16-month-old Tg2576 mice that have been crossed with a tau transgenic line harboring a triple-mutant tau (G272V, P310L, R406W) [34].”
From Characterization of a Mouse Model of Alzheimer’s Disease Expressing Aβ4-42 and Human Mutant Tau (2021) · cites this paper as [34]
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 [121]
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- Authors
- Ribé, E. M., Pérez, M., Puig, B., Gich, I., Lim, F., Cuadrado, M., Sesma, T., Catena, S., Sánchez, B., Nieto, M., Gómez-Ramos, P., Morán, M. A., Cabodevilla, F., Samaranch, L., Ortiz, L., Pérez, A., Ferrer, I., Avila, J., & Gómez-Isla, T.
- Affiliations
- Universidad de Navarra (ES)
- Centro de Biología Molecular Severo Ochoa (ES)
- Bellvitge University Hospital (ES)
- Hospital de Sant Pau (ES)
- Universidad Autónoma de Madrid (ES)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2005-12
- Volume
- 20
- Issue
- 3
- Pages
- 814-822
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2073724760
- Cited by
- 162
- References
- 28
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 5 · 2023: 6 · 2022: 9 · 2021: 10 · 2020: 12 · 2019: 3 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 16 · 2013: 8 · 2012: 8
- FWCI
- 5.00
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- Deposito Adademico Digital Universidad De Navarra (University of Navarra) (submittedVersion, other-oa)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- 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
- Alzheimer's disease, amyloid-beta, tau pathology, neurofibrillary degeneration, neuronal loss, Tg2576 mice, amyloid precursor protein, limbic system
- MeSH terms
- Alzheimer Disease, Animals, Brain, Disease Models, Animal, Female, Humans, Male, Mice, Transgenic, Mutation, Nerve Degeneration, Neurons, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, tau Proteins, Cell Death, Mice, Knockout, Mice, Plaque, Amyloid
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