Xanthurenic acid as a preclinical diagnostic marker and drug target of Alzheimer's disease in rats and mice and associated effects of Schizandrin

Alzheimer's disease (AD), a multipathogenic and irreversible neurodegenerative disease, threatens human health because a well-developed and compelling ‘theragnostic’ marker for monitoring biochemical events in this disease is lacking. In this experiment, high excretion of xanthurenic acid was found quantitatively before neurodegeneration in two classic AD models, including APP/PS1 transgenic mice and a chemical-induced rat model, based on metabolomic analysis coupled with UPLC-TQD-MS/MS. The discovery was beyond the recorded pathological process, including Aβ 42 deposition, astrocyte inflammatory hyperplasia and neuron loss, and it can be used not only as a diagnostic marker for the preclinical stage of AD but also as a target reflecting the disease-modifying effect of lead compounds for preventing AD. In this way, Schisandrin, a neuroprotective agent from Schisandra chinensis (Turcz.) Baill, was proven to adjust the level of xanthurenic acid in urine significantly in the present study. The predictability, treatment relevance, stability, reproducibility and accessibility of urine xanthurenic acid in our experiment indicates its feasibility as a potential diagnostic marker and drug target for the preclinical stage of AD.