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Presymptomatic alterations in energy metabolism and oxidative stress in the APP23 mouse model of Alzheimer disease

Item Type:Article
Title:Presymptomatic alterations in energy metabolism and oxidative stress in the APP23 mouse model of Alzheimer disease
Creators Name:Hartl, D. and Schuldt, V. and Forler, S. and Zabel, C. and Klose, J. and Rohe, M.
Abstract:Glucose hypometabolism is the earliest symptom observed in the brains of Alzheimer disease (AD) patients. In a former study, we analyzed the cortical proteome of the APP23 mouse model of AD at presymptomatic age (1 month) using a 2-D electrophoresis-based approach. Interestingly, long before amyloidosis can be observed in APP23 mice, proteins associated with energy metabolism were predominantly altered in transgenic as compared to wild-type mice indicating presymptomatic changes in energy metabolism. In the study presented here, we analyzed whether the observed changes were associated with oxidative stress and confirmed our previous findings in primary cortical neurons, which exhibited altered ADP/ATP levels if transgenic APP was expressed. Reactive oxygen species produced during energy metabolism have important roles in cell signaling and homeostasis as they modify proteins. We observed an overall up-regulation of protein oxidation status as shown by increased protein carbonylation in the cortex of presymptomatic APP23 mice. Interestingly, many carbonylated proteins, such as Vilip1 and Syntaxin were associated to synaptic plasticity. This demonstrates an important link between energy metabolism and synaptic function, which is altered in AD. In summary, we demonstrate that changes in cortical energy metabolism and increased protein oxidation precede the amyloidogenic phenotype in a mouse model for AD. These changes might contribute to synaptic failure observed in later disease stages, as synaptic transmission is particularly dependent on energy metabolism.
Keywords:Alzheimer Disease, APP23, Mouse Model, Energy Metabolism, Abeta, Proteome, Animals, Mice
Source:Journal of Proteome Research
Publisher:American Chemical Society
Page Range:3295-3304
Date:8 May 2012
Official Publication:https://doi.org/10.1021/pr300021e
PubMed:View item in PubMed

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