Impaired neuronal insulin signaling precedes Aβ42 accumulation in female AβPPsw/PS1ΔE9 mice

Chua, Li-Min, Lim, Mei-Li, Chong, Pey-Rou, Hu, Ze Ping, Cheung, Nam Sang and Wong, Boon-Seng 2012, Impaired neuronal insulin signaling precedes Aβ42 accumulation in female AβPPsw/PS1ΔE9 mice, Journal of alzheimer's disease, vol. 29, no. 4, pp. 783-791.

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Title Impaired neuronal insulin signaling precedes Aβ42 accumulation in female AβPPsw/PS1ΔE9 mice
Author(s) Chua, Li-Min
Lim, Mei-Li
Chong, Pey-Rou
Hu, Ze Ping
Cheung, Nam Sang
Wong, Boon-Seng
Journal name Journal of alzheimer's disease
Volume number 29
Issue number 4
Start page 783
End page 791
Total pages 9
Publisher IOS Press
Place of publication Amsterdam, The Netherlands
Publication date 2012
ISSN 1387-2877
1875-8908
Keyword(s) alzheimer's disease
amyloid
glucose transporter
insulin signaling
neurodegeneration
Summary Reduced glucose utilization is likely to precede the onset of cognitive deficits in Alzheimer's disease (AD). Similar aberrant glucose metabolism can also be detected in the brain of several AD mouse models. Although the cause of this metabolic defect is not well understood, it could be related to impaired insulin signaling that is increasingly being reported in AD brain. However, the temporal relationship between insulin impairment and amyloid-β (Aβ) biogenesis is unclear. In this study using female AβPPsw/PS1ΔE9 mice, we found that the level of Aβ40 was fairly constant in 6- to 15-month-old brains, whereas Aβ42 was only significantly increased in the 15-month-old brain. In contrast, increased levels of IRβ, IGF-1R, IRS1, and IRS-2, along with reduced glucose and insulin content, were detected earlier in the 12-month-old brains of AβPPsw/PS1ΔE9 mice. The reduction in brain glucose content was accompanied by increased GLUT3 and GLUT4 levels. Importantly, these changes precede the significant upregulation of Aβ42 level in the 15-month-old brain. Interestingly, reduction in the p85 subunit of PI3K was only apparent in the 15-month-old AβPPsw/PS1ΔE9 mouse brain. Furthermore, the expression profile of IRβ, IRS-2, and p85/PI3K in AβPPsw/PS1ΔE9 was distinct in wild-type mice of a similar age. Although the exact mechanisms underlining this connection remain unclear, our results suggest a possible early role for insulin signaling impairment leading to amyloid accumulation in AβPPsw/PS1ΔE9 mice.
Language eng
Field of Research 069999 Biological Sciences not elsewhere classified
Socio Economic Objective 970106 Expanding Knowledge in the Biological Sciences
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2012, IOS Press and the authors
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047037

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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Citation counts: TR Web of Science Citation Count  Cited 6 times in TR Web of Science
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Created: Mon, 13 Aug 2012, 13:03:21 EST

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