Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics
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 biof...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-12-01
|
| Series: | Metabolism Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589936821000499 |
| _version_ | 1818461747598589952 |
|---|---|
| author | Jonas Ellegaard Nielsen Raluca Georgiana Maltesen Jesper F. Havelund Nils J. Færgeman Charlotte Held Gotfredsen Karsten Vestergård Søren Risom Kristensen Shona Pedersen |
| author_facet | Jonas Ellegaard Nielsen Raluca Georgiana Maltesen Jesper F. Havelund Nils J. Færgeman Charlotte Held Gotfredsen Karsten Vestergård Søren Risom Kristensen Shona Pedersen |
| author_sort | Jonas Ellegaard Nielsen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T23:51:04Z |
| format | Article |
| id | doaj.art-ecfb0607ea694f328606f3b4d43b10a6 |
| institution | Directory Open Access Journal |
| issn | 2589-9368 |
| language | English |
| last_indexed | 2024-12-14T23:51:04Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Metabolism Open |
| spelling | doaj.art-ecfb0607ea694f328606f3b4d43b10a62022-12-21T22:43:15ZengElsevierMetabolism Open2589-93682021-12-0112100125Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomicsJonas Ellegaard Nielsen0Raluca Georgiana Maltesen1Jesper F. Havelund2Nils J. Færgeman3Charlotte Held Gotfredsen4Karsten Vestergård5Søren Risom Kristensen6Shona Pedersen7Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, DenmarkTranslational Radiation Biology and Oncology Laboratory, Centre for Cancer Research, Westmead Institute of Medical Research, Westmead, Australia; Department of Anaesthesia and Intensive Care, Aalborg University Hospital, Aalborg, DenmarkDepartment of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, DenmarkDepartment of Biochemistry and Molecular Biology, Villum Center for Bioanalytical Sciences, University of Southern Denmark, Odense, DenmarkDepartment of Chemistry, Technical University of Denmark, Kgs. Lyngby, DenmarkDepartment of Neurology, Aalborg University Hospital, Aalborg, DenmarkDepartment of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, DenmarkDepartment of Basic Medical Sciences, College of Medicine, Qatar University, Qatar Health, Doha, Qatar; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2589936821000499AlzheimerMetabolitesBloodExtracellular vesiclesMass spectrometryNuclear magnetic resonance |
| spellingShingle | Jonas Ellegaard Nielsen Raluca Georgiana Maltesen Jesper F. Havelund Nils J. Færgeman Charlotte Held Gotfredsen Karsten Vestergård Søren Risom Kristensen Shona Pedersen Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics Metabolism Open Alzheimer Metabolites Blood Extracellular vesicles Mass spectrometry Nuclear magnetic resonance |
| title | Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics |
| title_full | Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics |
| title_fullStr | Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics |
| title_full_unstemmed | Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics |
| title_short | Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics |
| title_sort | characterising alzheimer s disease through integrative nmr and lc ms based metabolomics |
| topic | Alzheimer Metabolites Blood Extracellular vesicles Mass spectrometry Nuclear magnetic resonance |
| url | http://www.sciencedirect.com/science/article/pii/S2589936821000499 |
| work_keys_str_mv | AT jonasellegaardnielsen characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT ralucageorgianamaltesen characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT jesperfhavelund characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT nilsjfærgeman characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT charlotteheldgotfredsen characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT karstenvestergard characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT sørenrisomkristensen characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics AT shonapedersen characterisingalzheimersdiseasethroughintegrativenmrandlcmsbasedmetabolomics |