Urinary and faecal metabolic characteristics in APP/PS1 transgenic mouse model of Alzheimer's disease with and without cognitive decline.

Alzheimer's disease (AD) has been considered to be a systematic metabolic disorder, but little information is available about metabolic changes in the urine and feces. In this study, we investigated urinary and faecal metabolic profiles in amyloid precursor protein/presenilin 1 (APP/PS1) mice at 3 and 9 months of age (3 M and 9 M) and age-matched wild-type (WT) mice by using 1H NMR-based metabolomics, and aimed to explore changes in metabolic pathways during amyloid pathology progression and identify potential metabolite biomarkers at earlier stage of AD. The results show that learning and memory abilities were impaired in APP/PS1 mice relative to WT mice at 9 M, but not at 3 M. However, metabolomics analysis demonstrates that AD disrupted metabolic phenotypes in the urine and feces of APP/PS1 mice at both 3 M and 9 M, including amino acid metabolism, microbial metabolism and energy metabolism. In addition, several potential metabolite biomarkers were identified for discriminating AD and WT mice prior to cognitive decline with the AUC values from 0.755 to 0.971, such as taurine, hippurate, urea and methylamine in the urine as well as alanine, leucine and valine in the feces. Therefore, our results not only confirmed AD as a metabolic disorder, but also contributed to the identification of potential biomarkers at earlier stage of AD.