Characterization of Metabolites in a Zebrafish Model of Alzheimer's Disease Supplemented with Mussel-Derived Plasmalogens by Ultraperformance Liquid Chromatography Q-Exactive Orbitrap Mass Spectrometry-Based Unbiased Metabolomics.

Plasmalogens (Pls) are bioactive substances enriched in the brain with a regulatory effect on Alzheimer's disease (AD), while their metabolomic influence accompanying AD and the underlying mechanisms remain unclear. Here, we extracted and purified Pls (purity of ≥90%) from mussels and applied unbiased metabolomics using ultraperformance liquid chromatography Q-Exactive Orbitrap mass spectrometry to analyze the variation of metabolites in the major metabolic pathways of AD and revealed the cognitive improvement effect of Pls using an experimental AD zebrafish model. The results showed that 37 differential endogenous metabolites were identified, among which glycerophosphocholine, choline, S-adenosylmethionine (SAM), l-glutamine, linoleic acid, 9(S)-HPODE, methionine, and creatine were the major abnormally regulated metabolites, and the first four metabolites were viewed as potential endogenous markers. This study suggested that systemic metabolic profiling could reveal the potential metabolic networks of AD and illuminated the protective effect of Pls on AD through biochemistry mechanisms and metabolic pathways.