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Age‐dependent dysregulation of brain amyloid precursor protein in the Ts65Dn Down syndrome mouse model
Author(s) -
Choi Jennifer H. K.,
Berger Jason D.,
Mazzella Matthew J.,
MoralesCorraliza Jose,
Cataldo Anne M.,
Nixon Ralph A.,
Ginsberg Stephen D.,
Levy Efrat,
Mathews Paul M.
Publication year - 2009
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06277.x
Subject(s) - amyloid precursor protein , down syndrome , immunoprecipitation , chromosome 21 , biology , endocrinology , western blot , metabolite , medicine , amyloid (mycology) , alzheimer's disease , gene , microbiology and biotechnology , disease , chromosome , genetics , botany
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.