Impaired Glutamatergic and GABAergic Function at Early Age in AβPPswe-PS1dE9 Mice: Implications for Alzheimer's Disease

Preclinical diagnosis of Alzheimer's disease is a major challenge. The present study evaluates glutamatergic and GABAergic neurotransmitter energetics at the age of 6 months in AβPPswe-PS1dE9 mouse model of Alzheimer's disease by using ¹H-[¹³C]-NMR spectroscopy together with infusion of [1,6-¹³C₂]glucose. NMR analysis suggested no significant derangement in neurochemical profile in AβPPswe-PS1dE9 mice. However, decrease in labeling of glutamate-C4, GABA-C2 and glutamine-C4 at early infusion-time together with no change in labeling at steady state from [1,6-¹³C₂]glucose indicates an impaired glutamatergic and GABAergic glucose oxidation and neurotransmitter cycle in AβPPswe-PS1dE9 mice. These findings may have implication in preclinical diagnosis of Alzheimer's disease.