Giuseppe Astarita (Presenter)
Georgetown University
Authorship: Giuseppe Paglia1,2, Markus Keller3, Matteo Stocchero4, Stefano Cacciatore5, Steven Lai6, Peggi Angel7, Markus Ralser8,9, Giuseppe Astarita6,10*
1. Center for Biomedicine, EURAC Research, Via Galvani 31, 39100 Bolzano, Italy 2. Center for Systems Biology, University of Iceland, Sturlugata 8, Reykjavik, Iceland 3. Department of Biochemistry, Un
| Short Abstract Alzheimer's disease (AD) is the most common cause of adult dementia, but the complete set of molecular changes accompanying this inexorable neurodegenerative disease remains still elusive. Here we used an unbiased lipidomics and metabolomics approach to survey frozen frontal cortex samples from clinically characterized AD patients (n=21) and age-matched controls (n=19). Our study highlights specific biochemical pathways that are altered in the brains from individuals with AD compared to control subjects, supporting future venues of investigations. |
Long Abstract
Alzheimer's disease (AD) is the most common cause of adult dementia, but the complete set of molecular changes accompanying this inexorable neurodegenerative disease remains still elusive. Here we conducted an unbiased investigation of the underlying biochemical alterations occurring in both lipid and polar metabolite metabolism in AD human brains. We used an integrated lipidomics and metabolomics approach to survey frozen frontal cortex samples from clinically characterized AD patients (n=21) and age-matched controls (n=19). Lipids and polar metabolites were extracted using a biphasic, liquid-liquid extraction procedure (CHCl3:MeOH:H2O, 2:1:1, v:v:v). Polar metabolites were separated using a hydrophobic interaction liquid chromatography (HILIC), whereas lipids using an integrated microfluidic device packed with reversed phase C18 before mass spectrometry (MS). Lipidomic and metabolomic analyses showed marked molecular differences between frontal cortices from AD patients and age-matched controls. Metabolomics pathway analysis was then used to incorporate the novel molecular information into the known biochemical pathways, which was then compared with the results of a metabolomics meta-analysis of previously published research in AD. Six metabolic pathways of the central metabolism as well as glycerophospholipid metabolism were found to be predominantly altered in AD brains. A marked dysregulation of the aspartate and glutamate metabolism was confirmed using more targeted metabolomic approaches and MS imaging. The altered metabolic pathways were further integrated with clinical data, showing various degrees of correlation of with parameters of dementia and AD pathology. Our study highlights specific biochemical pathways that are altered in the brains from individuals with AD compared from those from control subjects, with particular emphasis on the aspartate metabolism, supporting future venues of investigations.
References & Acknowledgements:
| Description | Y/N | Source |
| Grants | no | |
| Salary | yes | Waters Corp |
| Board Member | no | |
| Stock | no | |
| Expenses | no |
IP Royalty: no
| Planning to mention or discuss specific products or technology of the company(ies) listed above: | no |