Hypermetabolic State in the 7-Month-Old Triple Transgenic Mouse Model of Alzheimer'S Disease and the Effect of Lipoic Acid: A ¹³C-NMR Study

<jats:p> Alzheimer's disease (AD) is characterized by age-dependent biochemical, metabolic, and physiologic changes. These age-dependent changes ultimately converge to impair cognitive functions. This study was carried out to examine the metabolic changes by probing glucose and tricarboxylic acid cycle metabolism in a 7-month-old triple transgenic mouse model of AD (3×Tg-AD). The effect of lipoic acid, an insulin-mimetic agent, was also investigated to examine its ability in modulating age-dependent metabolic changes. Seven-month-old 3×Tg-AD mice were given intravenous infusion of [1-<jats:sup>13</jats:sup>C]glucose followed by an ex vivo<jats:sup>13</jats:sup>C nuclear magnetic resonance to determine the concentrations of <jats:sup>13</jats:sup>C-labeled isotopomers of glutamate, glutamine, aspartate, gamma aminobutyric acid, and N-acetylaspartate. An intravenous infusion of [1-<jats:sup>13</jats:sup>C]glucose+[1,2-<jats:sup>13</jats:sup>C]acetate was given for different periods of time to distinguish neuronal and astrocytic metabolism. Enrichments of glutamate, glutamine, and aspartate were calculated after quantifying the total (<jats:sup>12</jats:sup>C+<jats:sup>13</jats:sup>C) concentrations by high-performance liquid chromatography. A hypermetabolic state was clearly evident in 7-month-old 3×Tg-AD mice in contrast to the hypometabolic state reported earlier in 13-month-old mice. Hypermetabolism was evidenced by prominent increase of <jats:sup>13</jats:sup>C labeling and enrichment in the 3×Tg-AD mice. Lipoic acid feeding to the hypermetabolic 3×Tg-AD mice brought the metabolic parameters to the levels of nonTg mice. </jats:p>