Abstract
Background and Aim: Alzheimer's disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD.Methods: We recruited 107 participants including 23 healthy controls (HC), 21 amnestic mild cognitive impairment (aMCI), 24 non-amnestic mild cognitive impairment (naMCI) and 39 AD patients. Via liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis, we compared differences in serum lipid metabolites among these patient groups and further elucidated biomarkers that differentiate aMCI from HC.Results: There were significant differences of serum lipid metabolites among the groups, and 20 metabolites were obtained under negative ion mode from HC and aMCI comparison. Notably, 16:3 cholesteryl ester, ganglioside GM3 (d18:1/9z-18:1) and neuromedin B were associated with cognition and increased the predictive effect of aMCI to 0.98 as revealed by random forest classifier. The prediction model composed of MoCA score, 16:3 cholesteryl ester and ganglioside GM3 (d18:1/9z-18:1) had good predictive performance for aMCI. Glycerophospholipid metabolism was a pathway common among HC/aMCI and aMCI/AD groups.Conclusion: This study provides preliminary evidence highlighting that 16:3 cholesteryl ester were useful for AD disease monitoring while ganglioside GM3 (d18:1/9z-18:1) and neuromedin B discriminated aMCI from HC, which can probably be applied in clinic for early predicting of AD.
Highlights
Alzheimer’s disease (AD) is the commonest type of dementia and presents with a wide range of metabolic perturbations early in the disease process [1]
The post hoc analysis of healthy control (HC), mild cognitive impairment (MCI), and AD has been provided in the Supplementary Table 4
Thirteen retention. time-mass charge ratio (RT-MZ) types were significant in all 3 pairwise comparisons, while 9 types were significant in only one pairwise comparisons among the groups; namely between MCI and AD groups (Supplementary Table 5)
Summary
Alzheimer’s disease (AD) is the commonest type of dementia and presents with a wide range of metabolic perturbations early in the disease process [1]. A number of metabolomics studies have attempted to obtain from serum, plasma or whole blood specimens biomarkers useful for predicting AD. We subdivided MCI patients into aMCI and naMCI subgroups for further analysis and utilized liquid chromatography-mass spectrometry based serum untargeted lipidomics analysis to obtain raw data. This study aimed to determine whether there was any difference in serum metabolites among HC, MCI, and AD groups, and to elucidate potential biomarkers for predicting early AD. Alzheimer’s disease (AD) is the most common type of dementia and presents with metabolic perturbations early in the disease process. In order to explore biomarkers useful in predicting early AD, we compared serum metabolites among patients suffering different stages of AD
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