Age-related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice

Proton magnetic resonance spectroscopy (H-1-MRS) and the Morris water maze (MWM) have played an important role in Alzheimer's disease (AD) research. The aim of this study was to determine whether H-1-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. H-1-MRS was performed in 20 tg mice and 15 wild-type mice at 3,5 and 8 months of age. The concentration of N-acetylaspartate (NAA), glutamate (Glu), myo-inositol (ml), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr. Glu/Cr, ml/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The H-1-MRS revealed that ml levels in tg mice were significantly higher at 3 months of age compared to wt mice, while the NAA and Glu levels in 5- and 8-month-old tg mice were significantly decreased (p < 0.05). Additionally, significant cognitive changes only occurred at 8 months of age in APP/PS1 tg mice. These results indicated that metabolic changes preceded overt cognitive dysfunctions in early-stage AD, suggesting that H-1-MRS is a more sensitive biomarker for assessing early AD. (c) 2012 Elsevier B.V. All rights reserved.