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The combination of complementary metabolomic platforms to unravel Alzheimer's disease pathogenesis
1  Department of Chemistry, Faculty of Experimental Sciences. University of Huelva, Spain.


Alzheimer’s disease (AD) is the most common neurodegenerative disorder among older people, characterized by an insidious onset and a progressive decline of cognitive functions. Nowadays, there is no cure for AD mainly because its etiology is still unclear and current diagnostic tests show great limitations, including low sensitivity and specificity, as well as the impossibility to detect characteristic symptoms at early stages of disease. Thus, the main objective of this work was the optimization of complementary metabolomic approaches based on mass spectrometry in order to investigate AD pathogenesis and discover potential biomarkers for diagnosis. With the aim to get a comprehensive metabolome coverage, multiple analytical platforms were developed, including screening procedures based on direct mass spectrometry analysis and hyphenated approaches with orthogonal separation mechanisms such as liquid chromatography, gas chromatography and capillary electrophoresis. The application of these techniques to serum samples from patients suffering from Alzheimer’s disease and mild cognitive impairment enabled the identification of numerous metabolic alterations linked to pathogenesis of this disorder and its progression from pre-clinical stages, including abnormalities in the composition of membrane lipids, deficits in energy metabolism and neurotransmission, and oxidative stress, among others. Accordingly, it could be concluded that the combination of complementary metabolomic platforms allows studying etiology associated with Alzheimer’s disease in a deeper manner. See also slide presentation:

Keywords: metabolomics; Alzheimer's disease; mass spectrometry; serum
Comments on this paper
Juan Castillo-Garit
About enzyme regulation in AD
we are interested in know if you found important aspects about enzyme regulation in AD, as you know the levels of dopamine, serotonin, etc have diverse consecuences in neurodegenerative diseases. Can you tell us more about it? or can you send us any other matherial (papers, etc).
Raúl González-Domínguez
Dear Prof. Castillo Garit,
I didn’t perform enzymatic measurements because I had not the needed facilities for these purposes in my research group, but I considered previous works in this field in order to interpret my metabolomic data. However, it could obviously be a great idea to combine both measurements (in terms of a “multi-omic” approach) in order to get a deeper understanding about these dysregulations. Regarding the involvement of neurotransmitter systems in AD, we found decreased levels of numerous NTs (serotonin, dopamine) and their precursors (aromatic amino acids) in serum from AD patients, and these findings were additionally validated in blood and brain samples from APP/PS1 transgenic mice. If you are interested, you can find more information in previously published papers (ORCID 0000-0002-7640-8833).

Juan Castillo-Garit
Dear Prof. Raul Gonzalez-Dominguez
We nave developed several computational models to identify MAO inhibitors and also we are planining to develop new model to Ach and others with the aim of find new compounds with potential action as neuroprptectors. I´ll chec the papers soon,
Best Regards