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.
Keywords: Alzheimer’s disease, disease progression, membrane breakdown, metabolomics, mild cognitive impairment, pathological mechanisms.
Current Alzheimer Research
Title:Metabolomic-Driven Elucidation of Serum Disturbances Associated with Alzheimer's Disease and Mild Cognitive Impairment
Volume: 13 Issue: 6
Author(s): Raúl González-Domínguez, Francisco Javier Rupérez, Tamara García-Barrera, Coral Barbas and José Luis Gómez-Ariza
Affiliation:
Keywords: Alzheimer’s disease, disease progression, membrane breakdown, metabolomics, mild cognitive impairment, pathological mechanisms.
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.
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Cite this article as:
González-Domínguez Raúl, Rupérez Javier Francisco, García-Barrera Tamara, Barbas Coral and Gómez-Ariza Luis José, Metabolomic-Driven Elucidation of Serum Disturbances Associated with Alzheimer's Disease and Mild Cognitive Impairment, Current Alzheimer Research 2016; 13 (6) . https://dx.doi.org/10.2174/1567205013666160129095138
DOI https://dx.doi.org/10.2174/1567205013666160129095138 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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