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المؤلفNielsen, Jonas Ellegaard
المؤلفAndreassen, Trygve
المؤلفGotfredsen, Charlotte Held
المؤلفOlsen, Dorte Aalund
المؤلفVestergaard, Karsten
المؤلفMadsen, Jonna Skov
المؤلفKristensen, Søren Risom
المؤلفPedersen, Shona
تاريخ الإتاحة2024-03-13T10:02:35Z
تاريخ النشر2024-02-01
اسم المنشورMetabolomics
المعرّفhttp://dx.doi.org/10.1007/s11306-023-02078-8
الاقتباسNielsen, J. E., Andreassen, T., Gotfredsen, C. H., Olsen, D. A., Vestergaard, K., Madsen, J. S., ... & Pedersen, S. (2024). Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study. Metabolomics, 20(1), 12.‏
الرقم المعياري الدولي للكتاب15733882
معرّف المصادر الموحدhttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85181480177&origin=inward
معرّف المصادر الموحدhttp://hdl.handle.net/10576/53025
الملخصIntroduction: Alzheimer’s Disease (AD) is complex and novel approaches are urgently needed to aid in diagnosis. Blood is frequently used as a source for biomarkers; however, its complexity prevents proper detection. The analytical power of metabolomics, coupled with statistical tools, can assist in reducing this complexity. Objectives: Thus, we sought to validate a previously proposed panel of metabolic blood-based biomarkers for AD and expand our understanding of the pathological mechanisms involved in AD that are reflected in the blood. Methods: In the validation cohort serum and plasma were collected from 25 AD patients and 25 healthy controls. Serum was analysed for metabolites using nuclear magnetic resonance (NMR) spectroscopy, while plasma was tested for markers of neuronal damage and AD hallmark proteins using single molecule array (SIMOA). Results: The diagnostic performance of the metabolite biomarker panel was confirmed using sparse-partial least squares discriminant analysis (sPLS-DA) with an area under the curve (AUC) of 0.73 (95% confidence interval: 0.59–0.87). Pyruvic acid and valine were consistently reduced in the discovery and validation cohorts. Pathway analysis of significantly altered metabolites in the validation set revealed that they are involved in branched-chain amino acids (BCAAs) and energy metabolism (glycolysis and gluconeogenesis). Additionally, strong positive correlations were observed for valine and isoleucine between cerebrospinal fluid p-tau and t-tau. Conclusions: Our proposed panel of metabolites was successfully validated using a combined approach of NMR and sPLS-DA. It was discovered that cognitive-impairment-related metabolites belong to BCAAs and are involved in energy metabolism.
اللغةen
الناشرSpringer
الموضوعAlzheimer
Biomarker
Metabolites
Nuclear magnetic resonance
Serum
Single molecule array
العنوانSerum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study
النوعArticle
رقم العدد1
رقم المجلد20
dc.accessType Abstract Only


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