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Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease
Open accessAbstract
Transgenic mice carrying disease-linked forms of genes associated with Alzheimer disease often demonstrate deposition of the beta-amyloid as senile plaques and cerebral amyloid angiopathy. We have characterized the natural history of beta-amyloid deposition in APPswe/PS1dE9 mice, a particularly aggressive transgenic mouse model generated with mutant transgenes for APP (APPswe: KM594/5NL) and PS1 (dE9: deletion of exon 9). Ex vivo histochemistry showed Abeta deposition by 4 months with a progressive increase in plaque number up to 12 months and a similar increase of Abeta levels. In vivo multiphoton microscopy at weekly intervals showed increasing beta-amyloid deposition as CAA and plaques. Although first appearing at an early age, CAA progressed at a significantly slower rate than in the Tg2576 mice. The consistent and early onset of beta-amyloid accumulation in the APPswe/PS1dE9 model confirms its utility for studies of biochemical and pathological mechanisms underlying beta-amyloid deposition, as well as exploring new therapeutic treatments.
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“As previously shown, human APOE alleles targeted to APPSW/PS1dE9 mice reproduce their differential effect on the magnitude of Aβ plaque load [13] but do not delay onset of Aβ deposition compared to APPSW/PS1dE9 mice expressing native murine apoE [14].”
From Blocking the apoE/Aβ interaction ameliorates Aβ-related pathology in APOE ε2 and ε4 targeted replacement Alzheimer model mice (2014) · cites this paper as [14]
In the citing paper
“The APP SW /PS1 dE9 line represents a Tg model with enhanced disease phenotype, whereby the first plaques are detected by thioflavin-S at the age of 4 months.54”
From Blocking the Interaction between Apolipoprotein E and Aβ Reduces Intraneuronal Accumulation of Aβ and Inhibits Synaptic Degeneration (2013) · cites this paper as [54]
Citations
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Sperling, R. A., Jack, C. R., Black, S. E., Frosch, M. P., Greenberg, S. M., Hyman, B. T., Scheltens, P., Carrillo, M. C., Thies, W., Bednar, M. M., et al. (2011) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.05.2351 · Cited by 857
Self-citationSynchronous Hyperactivity and Intercellular Calcium Waves in Astrocytes in Alzheimer Mice
Kuchibhotla, K. V., Lattarulo, C. R., Hyman, B. T., & Bacskai, B. J. (2009) · Science · doi:10.1126/science.1169096 · Cited by 729
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García-Alloza, M., Borrelli, L. A., Rozkalne, A., Hyman, B. T., & Bacskai, B. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04613.x · Cited by 676
Self-citationAmyloid β-Induced Neuronal Hyperexcitability Triggers Progressive Epilepsy
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Metadata
- Authors
- Garcia-Alloza, M., Robbins, E. M., Zhang-Nunes, S. X., Purcell, S. M., Betensky, R. A., Raju, S., Prada, C., Greenberg, S. M., Bacskai, B. J., & Frosch, M. P.
- Affiliations
- Harvard University (US)
- Corresponding author
- Frosch, Matthew P.
- ORCID
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 2006-12
- Volume
- 24
- Issue
- 3
- Pages
- 516-524
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2005719973
- Cited by
- 744
- References
- 46
- Citations by year
- 2026: 36 · 2025: 28 · 2024: 39 · 2023: 28 · 2022: 41 · 2021: 46 · 2020: 53 · 2019: 43 · 2018: 57 · 2017: 44 · 2016: 45 · 2015: 49 · 2014: 47 · 2013: 51 · 2012: 42
- FWCI
- 10.38
- 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)
- Funders
- Chinese Academy of Agricultural Sciences
- National Institutes of Health
- National Institute on Aging (R01AG021084, AG021084, R01AG020570, AG 020570)
- National Institute of Biomedical Imaging and Bioengineering (EB 000768, R01EB000768)
- 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
- amyloid-beta deposition, APP/PS1 mice, Alzheimer's disease, transgenic mouse model, amyloid plaques, cerebral amyloid angiopathy, multiphoton microscopy, Tg2576 mice
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Mice, Neurologic Mutants, Mice, Transgenic, Tissue Distribution, Amyloid beta-Protein Precursor, Mice, Plaque, Amyloid
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