A multi-metabolite analysis of serum by 1H NMR spectroscopy: Early systemic signs of Alzheimer’s disease

There is a paucity of biomarkers for chronic obstructive pulmonary disease (COPD). Metabolomics were applied to a defined COPD patient cohort from the ECLIPSE study (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points). Results were correlated with accepted biomarkers for the disease.Baseline control serum (n566) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II (n570), III (n564) and IV (n544) COPD patients were analysed by proton nuclear magnetic resonance ( 1 H NMR). Liquid chromatography with tandem mass spectrometry (LC-MS/ MS) was used to confirm amino acid changes detected by 1 H NMR. Data were correlated with body composition, emphysema and systemic inflammation.1 H NMR identified decreased lipoproteins, N,N-dimethylglycine, and increased glutamine, phenylalanine, 3-methylhistidine and ketone bodies in COPD patients with decreased branchedchain amino acids (BCAAs) observed in GOLD stage IV patients. BCAAs, their degradation products, 3-methylhistidine, ketone bodies, and triglycerides were correlated negatively with cachexia and positively with systemic inflammation. Emphysema patients also displayed decreased serum creatine, glycine and N,N-dimethylglycine. LC-MS/MS confirmed 1 H NMR findings relating to BCAAs, glutamine and 3-methylhistidine in GOLD stage IV patients. NMR-based metabolomics characterised COPD patients based on systemic effects and lung function parameters. Increased protein turnover occurred in all COPD patients with increased protein degradation in individuals with emphysema and cachexia.

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“…: assigned from the literature of TUKIAINEN and co-workers [10,11]. + : assigned from GlaxoSmithKline database of standards (unpublished data).…”

Section: Resultsmentioning

confidence: 99%

Metabolic profiling detects biomarkers of protein degradation in COPD patients

et al. 2011

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“…Statistically significant changes in serum metabolite levels were found between control and MCI by holistic selforganizing map analysis based on the combination of the three spectra rather than by analysis at individual time points, suggesting that the combined changes of several metabolites can be descriptive while the changes in individuals metabolites are not [46] . In addition, the data set also reflects the complexity of serum biochemistry and cognitive decline, as well as various biochemical pathways underlying MCI [46] .…”

Section: Metabolomics Studies On MCI Patientsmentioning

confidence: 86%

“…In addition, the data set also reflects the complexity of serum biochemistry and cognitive decline, as well as various biochemical pathways underlying MCI [46] . The analyses also address the role of elevated glycoproteins in the risk for AD, supporting the view that the coexistence of inflammation and metabolic syndrome forms a high risk condition for cognitive decline [47] .…”

Section: Metabolomics Studies On MCI Patientsmentioning

confidence: 99%

“…Decreased NAA, glutamate, glutamine, taurine, γ-amino butyric acid, choline and phosphocholine, creatine, phosphocreatine and succinate; and increased lactate, aspartate, glycine and other amino-acids including alanine, leucine, iso-leucine, valine and watersoluble free fatty-acids (0.8-0.9 and 1.2-1.3 ppm) in six affected regions [35] Alterations in tyrosine, tryptophan, purine, and tocopherol pathways; reductions in norepinephrine and its metabolites [38] Nine potential diagnostic biomarkers (LPCs, trypto phan, dihydrosphingosine, phytosphingosine and hexadecasphinganine) identified for AD [41] Eight sphingomyelin species significantly lower in AD; two ceramide species (N16:0 and N21:0) increased in AD; ratios of ceramide to sphingomyelin species differed significantly between groups; both N20:2 SM and OH-N25:0 ceramides were correlated with MMSE in AD [43] Omega-3 fatty acids indicative of MCI; elevated glyco proteins may be a risk for AD [46] CSF, cerebrospinal fluid; LC-ECA, liquid chromatography-electrochemical array; LPC, lysophosphatidyl choline; MDMS-SL, multi-dimensional mass spectrometry-based shotgun lipidomics; MMSE, mini-mental state examination; MS, mass spectrometry; NAA, N-acetyl-L-aspartate; NMR, nuclear magnetic resonance spectroscopy; SM, sphingomyelin; UPLC, ultra-performance liquid chromatography.…”

Section: H-nmrmentioning

confidence: 99%

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Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer’s disease

Huang

Wang

et al. 2012

Neurosci. Bull.

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Although the pathogenesis of Alzheimer's disease (AD) is still not fully understood, it is acknowledged that intervention should be made at the early stage. Therefore, identifying biomarkers for the clinical diagnosis is critical.Metabolomics, a novel "omics", uses methods based on low-molecular-weight molecules, with high-throughput evaluation of a large number of metabolites that may lead to the identification of new disease-specific biomarkers and the elucidation of pathophysiological mechanisms. This review discusses metabolomics investigations of AD and potential future developments in this field.

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“…This analytical approach has been applied in AD investigation in a variety of applications as can be seen in Table 1. For instance NMR has been used to uncover AD metabolic biomarkers involved in specific metabolic pathways such as oxidative [76], lipid [77] and cholesterol [78] metabolism.…”

Section: Metabolomics In Admentioning

confidence: 99%

Metabolomics in the Study of Alzheimer's Disease

Ibáñez

Valdés

García‐Cañas

et al. 2014

Comprehensive Analytical Chemistry

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With an increasing aging population, Alzheimer's disease (AD) has become a social and economic problem to societies worldwide, affecting millions of people. However, pathophysiological events associated with AD are not well elucidated yet and current definitive diagnosis is only obtained after death through examination of brain tissue. In the last years, Metabolomics has been demonstrated to provide deep insights into the full complexity of the disease phenotype and has been established as a promising approach to provide disease-specific metabolite signatures. The incipient application of Metabolomics may potentially contribute in the elucidation of AD physiopathological processes and ideally may offer therapeutic/preventing mechanisms to slow or reverse AD progress. In this chapter non-targeted metabolomics approaches applied to AD investigation are described.

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A multi-metabolite analysis of serum by 1H NMR spectroscopy: Early systemic signs of Alzheimer’s disease

Cited by 104 publications

References 22 publications

Metabolic profiling detects biomarkers of protein degradation in COPD patients

Metabolic profiling detects biomarkers of protein degradation in COPD patients

Metabolomics: a novel approach to identify potential diagnostic biomarkers and pathogenesis in Alzheimer’s disease

Metabolomics in the Study of Alzheimer's Disease

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