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

Proton magnetic resonance spectroscopy (1H-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 1H-MRS and the MWM can detect for early AD in APP/PS1 transgenic (tg) mice. 1H-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 (mI), choline (Cho) and creatine (Cr) in the hippocampus were measured, and the NAA/Cr, Glu/Cr, mI/Cr and Cho/Cr ratios were quantified. Additionally, the spatial learning and memory of the mice were evaluated by MWM. The 1H-MRS revealed that mI 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 1H-MRS is a more sensitive biomarker for assessing early AD.

► 1H-MRS and behavioral testing were performed in different age of APP/PS1 mice.
► The mI levels were significantly higher from 3 months of age in APP/PS1 mice.
► The NAA and Glu level were significantly decreased at 5–8 months of age in APP/PS1 mice.
► Changes in spatial learning and memory only occurred at 8-month-old APP/PS1 mice.
► Metabolic changes in brain preceded overt cognitive dysfunctions in early AD.