2021 年 5 巻 1 号 p. 11-21
Metabolic pathways are potential diagnostic markers for the early diagnosis of age-related cognitive decline due to Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB). Investigating the minute fluctuations of metabolite concentration or the ratios in cerebrospinal fluid (CSF) and serum that are reflected in brain disorders could lead to identify a useful biomarker candidate for the differential diagnosis between AD and DLB. Most metabolites are hydrophilic, so they were measured as 9-fluorenylmethyl chloroformate (FMOC) derivatives simultaneously using a liquid chromatography based on C18 column. The aim of this study was to validate and apply a simple and effective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of metabolites in CSF and serum samples from AD and DLB patients with confirmed diagnoses based on brain pathology. To evaluate the diversity of ninety-nine amine-mediated metabolic patterns and pathways, we identified possible metabolites that contributed to and mutually influenced principal component analysis with integrated analytes. The concentrations of several analytes differed significantly between the AD and DLB groups. The trends in the concentrations of intermediates in the amine metabolic pathway indicated an increase or decrease in β-alanine metabolism. The common metabolic patterns in the CSF and serum of AD and DLB patients included elevated levels of cystathionine, 3-hydroxykynurenine, 3-methoxytyramine, NG,NG-dimethyl-l-arginine, glutamate, uracil, and polyamines. The concentrations of cadaverine, arginine, and acetyllysine were lower. The results of our metabolic pathway analysis indicated that neurodegeneration would be involved peripheral β-alanine metabolites. Assessing comprehensively several metabolites identified using widely targeted metabolomics as multi-biomarker candidates would be effective technique to provide novel insights on neuroscience research.
