title: Metabolomic-Driven Elucidation of Serum Disturbances Associated with Alzheimer's Disease and Mild Cognitive Impairment.
abstract: Numerous efforts have been made in the last years to discover potential biomarkers of Alzheimer's disease and its progression from mild cognitive impairment, considered as an intermediate phase in the development of Alzheimer's disease from normal aging. However, there is still a considerable lack of understanding about pathological mechanisms underlying to disease. In the present study, serum metabolomics based on ultra-high-performance liquid chromatographymass spectrometry was applied to investigate metabolic differences between subjects with Alzheimer's disease and mild cognitive impairment, as well as healthy controls. The most important findings can be associated with impaired metabolism of phospholipids and sphingolipids leading to membrane breakdown, wherein the nature of the fatty acids contained in the structure in terms of acyl chain length and degree of unsaturation appears to play a crucial role. Furthermore, several discriminant metabolites were found for the first time in relation to known pathological processes associated with Alzheimer's disease, such as the accumulation of acylcarnitines in relation to mitochondrial dysfunction, decreased levels of oleamide and monoglycerides as a result of defects in endocannabinoid system, or increased serum phenylacetylglutamine, which could reveal alterations in glutamine homeostasis. Therefore, these results represent a suitable approximation to understand the pathogenesis and progression of the disease.
authors.forename: Raúl
authors.initials: R
authors.lastname: González-Domínguez
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Rupérez
authors.forename: Tamara
authors.initials: T
authors.lastname: García-Barrera
authors.forename: Coral
authors.initials: C
authors.lastname: Barbas
authors.affiliation: Department of Chemistry and CC.MM, Faculty of Experimental Science, University of Huelva, Campus de El Carmen. 21007 Huelva, Spain. ariza@uhu.es.
authors.forename: José Luis
authors.initials: JL
authors.lastname: Gómez-Ariza
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001774:Blood Chemical Analysis; D002851:Chromatography, High Pressure Liquid; D060825:Cognitive Dysfunction / Q000097:blood*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome
chemical_list: D015415:Biomarkers