Abstract
Hydrophilic metabolites are closely involved in multiple primary metabolic pathways and, consequently, play an essential role in the onset and progression of multifactorial human disorders, such as Alzheimer’s disease. This review article provides a comprehensive revision of the literature published on the use of mass spectrometry-based metabolomics platforms for approaching the central metabolome in Alzheimer’s disease research, including direct mass spectrometry, gas chromatography-mass spectrometry, hydrophilic interaction liquid chromatography-mass spectrometry, and capillary electrophoresis-mass spectrometry. Overall, mounting evidence points to profound disturbances that affect a multitude of central metabolic pathways, such as the energy-related metabolism, the urea cycle, the homeostasis of amino acids, fatty acids and nucleotides, neurotransmission, and others.
Highlights
Area of Pediatrics, Department of Child and Mother Health and Radiology, Medical School, University of Cádiz, 11002 Cádiz, Spain biomedicines9030298
Orthogonal analytical tools are crucial to approach this essential piece of the human metabolome puzzle, namely direct mass spectrometry (DMS), gas chromatography-mass spectrometry (GC-MS), hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS), and capillary electrophoresis-mass spectrometry (CE-MS)
The authors reported an accumulation of diacylglycerols, free fatty acids, and ceramides in Alzheimer’s disease (AD) serum, which is in line with the upregulated degradation of membrane lipids that was hypothesized in previous DMS studies, as well as other disturbances related to the monoaminergic neurotransmission and the urea cycle
Summary
Alzheimer’s disease (AD) is nowadays a major health problem due to the dramatic population aging worldwide. DMS fingerprinting, based on the direct introduction of the sample extracts into the mass spectrometer, shows great utility for high-throughput and comprehensive metabolomics analysis thanks to the lack of a chromatographic or electrophoretic separation prior to MS detection, which inherently bias the method coverage [12] This screening tool suffers from considerable ion suppression and the impossibility of resolving isomeric metabolites, which make the use of complementary approaches mandatory. Among MS-based hyphenated methods, GC-MS has been widely employed in metabolomics because of its reproducibility, chromatographic resolution, sensitivity, and selectivity [13] This technique usually requires the application of a derivatization process before the analysis for increasing the volatility and thermal stability of metabolites, enabling the profiling of numerous low molecular weight central metabolites, such as amino acids, sugars, organic and fatty acids, amines, and many other primary metabolites.
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