Regional metabolic alteration of Alzheimer's disease in mouse brain expressing mutant human APP-PS1 by 1H HR-MAS

Abstract

This study aimed to find the most sensitive brain region of APP-PS1 mice in early-stage Alzheimer's disease (AD) and to compare the findings with wild-type mouse brain using (1)H high resolution magic angle spectroscopy (HR-MAS). At 18 and 35 weeks of age, the object recognition test was performed with both APP-PS1 and wild-type mice, and the metabolite concentrations were measured in six brain regions at 38-42 weeks using (1)H HR-MAS. Compared to that of wild-type mice, the memory index of the APP-PS1 mice at 18 weeks was not significantly different; however, the memory index of the APP-PS1 mice at 35 weeks was significantly lower. Similar to the results of the (1)H HR-MAS, the [N-acetyl aspartate (NAA)+acetate (Acet)] level in APP-PS1 mice was decreased in the hippocampus and temporal cortex, and the myo-inositol (mIns) level was increased in the entire brain. In addition, scyllo-inositol (sIns) was also elevated in the frontal, occipital, and parietal cortices, hippocampus and thalamus. These findings demonstrated that the behavioral abnormalities of the APP-PS1 mice started at about 30 weeks of age and that the hippocampus and temporal cortex were the most sensitive regions during early-stage AD. In addition, the results of this study confirmed that an increase of mIns and sIns precedes the reduction of the NAA level. These findings demonstrated that the metabolism of the APP-PS1 mouse was associated with early-stage AD. Furthermore, the regional neurochemical profile of APP-PS1 mouse can be used to investigate the pathophysiological mechanisms associated with AD.