Metabolic fate of glucose in the brain of APP/PS1 transgenic mice at 10 months of age: a 13 C NMR metabolomic study

Abstract

Alzheimer's disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using ¹³C NMR metabolomics in combination with intravenous [1-¹³C]-glucose infusion in APP/PS1 transgenic mouse model of amyloid pathology at 10 months of age. We found that brain glucose was significantly accumulated in APP/PS1 mice relative to wild-type (WT) mice. Reductions in ¹³C fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, γ-aminobutyric acid and aspartate) from [1-¹³C]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the ¹³C-enrichments of the C3 of alanine were significantly lower and the C3 of lactate have a tendency to be lower in the brain of APP/PS1 mice than WT mice. Taken together, the development of amyloid pathology could cause a reduction in glucose utilization and further result in decreases in energy and neurotransmitter metabolism as well as the lactate-alanine shuttle in the brain.

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