Détail du document
Identifiant
doi:10.1007/s11306-023-02078-8...
Auteur
Nielsen, Jonas Ellegaard Andreassen, Trygve Gotfredsen, Charlotte Held Olsen, Dorte Aalund Vestergaard, Karsten Madsen, Jonna Skov Kristensen, Søren Risom Pedersen, ShonaLangue
enEditeur
Springer
Catégorie
Life Sciences
Année
2024
Date de référencement
10/01/2024
Mots clés
alzheimer metabolites biomarker serum nuclear magnetic resonance single molecule array panel involved adRésumé
Introduction 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.
Nielsen, Jonas Ellegaard,Andreassen, Trygve,Gotfredsen, Charlotte Held,Olsen, Dorte Aalund,Vestergaard, Karsten,Madsen, Jonna Skov,Kristensen, Søren Risom,Pedersen, Shona, 2024, Serum metabolic signatures for Alzheimer’s Disease reveal alterations in amino acid composition: a validation study, Springer
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