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Cited by 83Alzheimer's disease research and treatmentsDown syndrome and intellectual disability researchDementia and Cognitive Impairment Research

Age-dependent dysregulation of brain amyloid precursor protein in the Ts65Dn down syndrome mouse model

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Choi, Jennifer H. K., Berger, Jason D., Mazzella, Matthew J., Morales‐Corraliza, Jose, Cataldo, Anne M., Nixon, Ralph A., Ginsberg, Stephen D., Levy, Efrat +1 more·2009·Journal of Neurochemistry
DOI 10.1111/j.1471-4159.2009.06277.xPMC PMC2744432
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Abstract

Individuals with Down syndrome develop β‐amyloid deposition characteristic of early‐onset Alzheimer’s disease (AD) in mid‐life, presumably because of an extra copy of the chromosome 21‐located amyloid precursor protein (App) gene. App mRNA and APP metabolite levels were assessed in the brains of Ts65Dn mice, a mouse model of Down syndrome, using quantitative PCR, western blot analysis, immunoprecipitation, and ELISAs. In spite of the additional App gene copy, App mRNA, APP holoprotein, and all APP metabolite levels in the brains of 4‐month‐old trisomic mice were not increased compared with the levels seen in diploid littermate controls. However starting at 10 months of age, brain APP levels were increased proportional to the App gene dosage imbalance reflecting increased App message levels in Ts65Dn mice. Similar to APP levels, soluble amino‐terminal fragments of APP (sAPPα and sAPPβ) were increased in Ts65Dn mice compared with diploid mice at 12 months but not at 4 months of age. Brain levels of both Aβ40 and Aβ42 were not increased in Ts65Dn mice compared with diploid mice at all ages examined. Therefore, multiple mechanisms contribute to the regulation towards diploid levels of APP metabolites in the Ts65Dn mouse brain.

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  • Discordant outcomes between Dyrk1a RNA and protein expression in brain have been reported in older male Ts65Dn mice, although these comparisons came from different experiments.

    “Discordant outcomes between Dyrk1a RNA and protein expression in brain have been reported in older male Ts65Dn mice, although these comparisons came from different experiments (Ahmed et al., 2012; Choi et al., 2009; Sultan et al., 2007).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Choi et al., 2009

    The Results section reports increased DYRK1A mRNA in brain tissue from 12-month-old Ts65Dn mice, supporting the older-mouse RNA part of the claim. The paper does not report DYRK1A protein measurements or establish the claimed RNA–protein discordance; the cited passages also do not specify that these mice were male. No page number is available in our copy. (LLM, conf=0.86)

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  • Ts65Dn mouse brain/tissue at 5 months of age yielded no difference in Dyrk1a mRNA expression, but at 12 months Dyrk1a expression was elevated in Ts65Dn mice compared to controls.

    “Ts65Dn mouse brain/tissue at 5 months of age yielded no difference in Dyrk1a mRNA expression, but at 12 months Dyrk1a expression was elevated in Ts65Dn mice compared to controls (Choi et al., 2009).”

    From Sex-specific developmental alterations in DYRK1A expression in the brain of a Down syndrome mouse model (2024) · cites this paper as Choi et al., 2009

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Authors
Choi, J. H. K., Berger, J. D., Mazzella, M. J., Morales‐Corraliza, J., Cataldo, A. M., Nixon, R. A., Ginsberg, S. D., Levy, E., & Mathews, P. M.
Affiliations
  • Nathan Kline Institute for Psychiatric Research (US)
  • Harvard University (US)
ORCID
Venue
Journal of Neurochemistry
Publisher
Wiley
Published
2009-09
Volume
110
Issue
6
Pages
1818-1827
ISSN
  • 0022-3042 (ISSN-L)
  • 1471-4159
DOI
10.1111/j.1471-4159.2009.06277.x
PMC
PMC2744432
OpenAlex
W2020822926
Cited by
83
References
6
Citations by year
2025: 3 · 2024: 6 · 2023: 7 · 2022: 7 · 2021: 3 · 2020: 2 · 2019: 6 · 2018: 6 · 2017: 6 · 2016: 3 · 2015: 4 · 2014: 4 · 2013: 6 · 2012: 12
FWCI
4.43
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Journal of Neurochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institute on Aging (AG017617, P01AG014449, R01AG043375, AG029787, P01AG017617, F31AG029787)
  • National Institute of Neurological Disorders and Stroke (NS045205, R01NS045205)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Down syndrome, Ts65Dn mouse model, amyloid precursor protein, trisomy, soluble APP alpha, amyloid-beta, Alzheimer's disease, brain amyloid deposition
MeSH terms
Superoxide Dismutase-1, Dyrk Kinases, Aging, Animals, Brain, Disease Models, Animal, Down Syndrome, Enzyme-Linked Immunosorbent Assay, Gene Expression Regulation, Mice, Inbred C57BL, Mice, Transgenic, Protein-Tyrosine Kinases, RNA, Messenger, Superoxide Dismutase, Amyloid beta-Protein Precursor, Protein Serine-Threonine Kinases, Mice

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