Widely targeted metabolomics approaches to investigate dysregulation of multiple metabolites in the serum of triple transgenic Alzheimer's disease male mice

<strong>Introduction</strong> Alzheimer's disease (AD) is considered to be a multifactorial neurodegenerative disease that lacks effective drugs. <strong>Objective</strong> Pathological changes in the brain can be reflected in blood metabolites that are expected to explain the disease mechanisms or be candidate biomarkers. <strong>Methods</strong> Targeted metabolomics was used to quantify 256 metabolites in serum of triple transgenic AD (3×Tg-AD) male mice. <strong>Resutls</strong> Compared with control, 49 metabolites involved in bioamines and nucleoside analogues were identified as differential metabolites. They mainly were associated with purine, pyrimidine, tryptophan, cysteine and methionine and glycerophospholipid metabolism, of which the significant ones included decreased serum levels of adenosine, serotonin, N-acetyl-5-hydroxytryptamine, S-adenosine-L-homocysteine, and CDP-choline, and increased serum levels of S-adenosine-L-methionine, acetylcholine, and trimethylamine-N-oxide in AD mice. <strong>Conclusion</strong> The results revealed the changes of neuromodulators in serum, suggesting that dysregulated metabolites in periphery in AD mice may be related to the disturbances in neuroinhibition, the serotonergic system, sleep function, the cholinergic system, and the gut microbiota. The study proposed the possibility of developing peripheral biomarkers in early AD.