High throughput multiorgan metabolomics in the APP/PS1 mouse model of Alzheimer's disease

Metabolomics has demonstrated a great potential for the study of pathological mechanisms occurring in brain from Alzheimer's disease patients and transgenic models. However, its application to peripheral samples is not so common, although it can provide interesting information about systemic abnormalities underlying to disease. This work represents the first metabolomic investigation of multiple peripheral organs (liver, kidney, spleen, and thymus) from the APP/PS1 mice by using a high-throughput approach based on direct infusion MS. Our findings demonstrated that these organs suffer significant metabolic impairments related to energy metabolism (e.g. glycolysis, Krebs cycle, -oxidation), lipid homeostasis (e.g. cellular membrane breakdown and fatty acid metabolism), degradation of nucleotides, oxidative stress, hyperammonemia, and metabolism of amino acids. It is noteworthy that many of these alterations have been previously described in brain, confirming the systemic character of this neurodegenerative disorder and the utility of peripheral samples to understand its pathogenesis.