Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics
| Autor: | Karsten Vestergård, Jesper F. Havelund, Nils J. Færgeman, Shona Pedersen, Charlotte Held Gotfredsen, Raluca Maltesen, Søren Risom Kristensen, Jonas Ellegaard Nielsen |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Purine
p-tau Phospho-tau Aβ Amyloid-β Physiology Guanosine QD415-436 Pharmacology Biochemistry ROC Receiver operating characteristics Nuclear magnetic resonance MMSE Mini-mental state examination chemistry.chemical_compound Metabolomics Valine medicine Metabolites sPLS-DA Sparse partial least squared discriminant analysis QP1-981 FAQ Functional activities questionnaire Inosine AD Alzheimer's Disease EVs Extracellular vesicles chemistry.chemical_classification CSF Cerebrospinal fluid PCA Principal component analysis Mass spectrometry CNS Central nervous system business.industry CV Cross-validation MCI Mild cognitive impairment General Medicine Metabolism Extracellular vesicles AUC Area under the curve BBB Blood-brain barrier Extracellular vehicles Fold change t-tau Total-tau Amino acid ACE Addenbrooke's cognitive examination Blood chemistry Alzheimer FDR False discovery rate business BCAA Branched-chain amino acid Articles from the Clinical Metabolomics Special Issue medicine.drug |
| Zdroj: | Metabolism Open, Vol 12, Iss, Pp 100125-(2021) Nielsen, J E, Maltesen, R G, Havelund, J F, Færgeman, N J, Gotfredsen, C H, Vestergård, K, Kristensen, S R & Pedersen, S 2021, ' Characterising Alzheimer's disease through integrative NMR-and LC-MS-based metabolomics ', Metabolism Open, vol. 12, 100125 . https://doi.org/10.1016/j.metop.2021.100125 Nielsen, J E, Maltesen, R G, Havelund, J F, Færgeman, N J, Gotfredsen, C H, Vestergård, K, Kristensen, S R & Pedersen, S 2021, ' Characterising Alzheimer's disease through integrative NMR-and LC-MS-based metabolomics ', Metabolism open, vol. 12, 100125 . https://doi.org/10.1016/j.metop.2021.100125 Metabolism Open |
| ISSN: | 2589-9368 |
| Popis: | Background: Alzheimer's Disease (AD) is a complex and multifactorial disease and novel approaches are needed to illuminate the underlying pathology. Metabolites comprise the end-product of genes, transcripts, and protein regulations and might reflect disease pathogenesis. Blood is a common biofluid used in metabolomics; however, since extracellular vesicles (EVs) hold cell-specific biological material and can cross the blood-brain barrier, their utilization as biological material warrants further investigation. We aimed to investigate blood- and EV-derived metabolites to add insigts to the pathological mechanisms of AD.Methods: Blood samples were collected from 10 AD and 10 Mild Cognitive Impairment (MCI) patients, and 10 healthy controls. EVs were enriched from plasma using 100,000×g, 1 h, 4 °C with a wash. Metabolites from serum and EVs were measured using liquid chromatography-mass spectrometry (LC-MS) and nuclear magnetic resonance (NMR) spectroscopy. Multivariate and univariate analyses were employed to identify altered metabolites in cognitively impaired individuals.Results: While no significant EV-derived metabolites were found differentiating patients from healthy individuals, six serum metabolites were found important; valine (p = 0.001, fold change, FC = 0.8), histidine (p = 0.001, FC = 0.9), allopurinol riboside (p = 0.002, FC = 0.2), inosine (p = 0.002, FC = 0.3), 4-pyridoxic acid (p = 0.006, FC = 1.6), and guanosine (p = 0.004, FC = 0.3). Pathway analysis revealed branched-chain amino acids, purine and histidine metabolisms to be downregulated, and vitamin B6 metabolism upregulated in patients compared to controls.Conclusion: Using a combination of LC-MS and NMR methodologies we identified several altered mechanisms possibly related to AD pathology. EVs require additional optimization prior to their possible utilization as a biological material for AD-related metabolomics studies. |
| Databáze: | OpenAIRE |
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