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

Alzheimer's disease (AD) has been associated with the disturbance of brain glucose metabolism. The present study investigates brain glucose metabolism using C-13 NMR metabolomics in combination with intravenous [1-C-13]-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 C-13 fluxes into the specific carbon sites of tricarboxylic acid (TCA) intermediate (succinate) as well as neurotransmitters (glutamate, glutamine, gamma-aminobutyric acid and aspartate) from [1-C-13]-glucose were also detected in the brain of APP/PS1 mice. In addition, our results reveal that the C-13-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.