Metabolomic study of lipids in serum for biomarker discovery in Alzheimer's disease using direct infusion mass spectrometry

• Direct infusion mass spectrometry allows comprehensive lipidomic fingerprinting.
• Numerous lipids and metabolites are altered in serum of Alzheimer's disease.
• Potential biomarkers can be associated with important hallmarks of Alzheimer's disease.
• Membrane breakdown highlights as a key factor in development of Alzheimer's disease.
• Several novel biomarkers were found: diacylglycerols, oleamide and other metabolites.

In this study, we demonstrated the potential of direct infusion mass spectrometry for the lipidomic characterization of Alzheimer's disease. Serum samples were extracted for lipids recovery, and directly analyzed using an electrospray source. Metabolomic fingerprints were subjected to multivariate analysis in order to discriminate between groups of patients and healthy controls, and then some key-compounds were identified as possible markers of Alzheimer's disease. Major differences were found in lipids, although some low molecular weight metabolites also showed significant changes. Thus, important metabolic pathways involved in neurodegeneration could be studied on the basis of these perturbations, such as membrane breakdown (phospholipids and diacylglycerols), oxidative stress (prostaglandins, imidazole and histidine), alterations in neurotransmission systems (oleamide and putrescine) and hyperammonaemia (guanidine and arginine). Moreover, it is noteworthy that some of these potential biomarkers have not been previously described for Alzheimer's disease.

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