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

被引：64

作者：

Choi, Jennifer H. K. ^{[1
,2
]}

Berger, Jason D.

Mazzella, Matthew J.

Morales-Corraliza, Jose ^{[3
]}

Cataldo, Anne M. ^{[6
,7
,8
]}

Nixon, Ralph A. ^{[3
,5
]}

Ginsberg, Stephen D. ^{[2
]}

Levy, Efrat ^{[3
,4
]}

Mathews, Paul M. ^{[3
]}

机构：

[1] NYU, Sch Med, Nathan Kline Inst, Ctr Dementia Res, Orangeburg, NY 10962 USA

[2] NYU, Sch Med, Dept Physiol & Neurosci, Orangeburg, NY 10962 USA

[3] NYU, Sch Med, Dept Psychiat, Orangeburg, NY 10962 USA

[4] NYU, Sch Med, Dept Pharmacol, Orangeburg, NY 10962 USA

[5] NYU, Sch Med, Dept Cell Biol, Orangeburg, NY 10962 USA

[6] McLean Hosp, Mailman Res Ctr, Lab Mol Neuropathol, Belmont, MA 02178 USA

[7] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA

[8] Harvard Univ, Sch Med, Dept Neuropathol, Boston, MA 02115 USA

来源：

JOURNAL OF NEUROCHEMISTRY | 2009年 / 110卷 / 06期

关键词：

Alzheimer's disease; amyloid precursor protein; animal model; Down syndrome; trisomy; NERVE GROWTH-FACTOR; ALZHEIMERS-DISEASE; GENE-EXPRESSION; RETROGRADE TRANSPORT; RNA AMPLIFICATION; APP; NEURONS; ABNORMALITIES; MICE; NGF;

D O I：

10.1111/j.1471-4159.2009.06277.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Individuals with Down syndrome develop beta-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 (sAPP alpha and sAPP beta) were increased in Ts65Dn mice compared with diploid mice at 12 months but not at 4 months of age. Brain levels of both A beta 40 and A beta 42 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.

引用

页码：1818 / 1827

页数：10

共 51 条

[1] Terminal continuation (TC) RNA amplification without second strand synthesis [J].