Journal article
Characterising Alzheimer's disease through integrative NMR- and LC-MS-based metabolomics
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. 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. 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. 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.
| Language: | English |
|---|---|
| Publisher: | Elsevier |
| Year: | 2021 |
| Pages: | 100125 |
| ISSN: | 25899368 |
| Types: | Journal article |
| DOI: | 10.1016/j.metop.2021.100125 |
| ORCIDs: | 0000-0001-7261-5280 , 0000-0003-2332-2312 and Gotfredsen, Charlotte Held |
Alzheimer Blood Extracellular vehicles Mass spectrometry Metabolites Nuclear magnetic resonance
ACE, Addenbrooke's cognitive examination AD, Alzheimer's Disease AUC, Area under the curve Aβ, Amyloid-β BBB, Blood-brain barrier BCAA, Branched-chain amino acid Biochemistry CNS, Central nervous system CSF, Cerebrospinal fluid CV, Cross-validation EVs, Extracellular vesicles Extracellular vesicles FAQ, Functional activities questionnaire FDR, False discovery rate MCI, Mild cognitive impairment MMSE, Mini-mental state examination PCA, Principal component analysis Physiology QD415-436 QP1-981 ROC, Receiver operating characteristics p-tau, Phospho-tau sPLS-DA, Sparse partial least squared discriminant analysis t-tau, Total-tau
