Application of IVDr NMR spectroscopy to stratify Parkinson’s disease with absolute quantitation of blood serum metabolites and lipoproteins
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Le résumé fourni par la source
The challenge of early detection and stratification in Parkinson's disease (PD) is urgent due to the current emergence of mechanism-based disease-modifying treatments. In here, metabolomic and lipidomic parameters obtained by a standardized and targeted in vitro diagnostic research (IVDr) platform have a significant potential to address therapy-related questions and generate improved biomarker panels. Our study aimed to use IVDr nuclear magnetic resonance (NMR) spectroscopy to quantify metabolites and lipoproteins in PD blood serum from different cohorts to stratify metabolically driven subtypes of idiopathic and genetic PD. Serum aliquots from three neurodegeneration biobank cohorts (287 samples in total, including 62 PD patient samples with GBA mutation, 98/43 PD patient samples of early/late stages of disease duration, 20 PD samples from patients with mutations in recessive PD genes and some smaller subgroups of mitochondrial and double mutation cases) were prepared and analyzed with IVDr NMR spectroscopy, covering 39 blood serum metabolites and 112 lipoprotein parameters. Uni- and multivariate statistics were used to identify metabolism-driven changes under consideration of typical confounders such as age, sex and disease duration and set into context with clinical biomarkers such as CSF concentrations of alpha-synuclein, neurofilament light chain, and tau protein. Based on the different PD subgroups we performed a total of eight different comparisons. Highlights from these comparisons include increased citrate and dimethylglycine with a decrease of creatinine and methionine in healthy controls and early PD group compared to GBA, PD late and recessive PD. We furthermore identified decreased HDL-3 free cholesterol in genetic PD cases compared to sporadic subject samples (sum of the PD early and PD late groups). Considering medication, we found that the levodopa equivalent daily dose (LEDD) is mostly positively correlated with tyrosine and citrate in sporadic PD compared to pyruvate and phenylalanine in genetic PD. Cerebrospinal fluid levels of alpha-synuclein were negatively correlated with alanine. Further metabolites and lipoproteins with discriminatory power for double mutation PD cases involved ornithine, 2-aminobutyrate and 2-hydroxybutyrate as well as for mitochondrial phenotypes via LDL phospholipid, apolipoprotein and cholesterol subfractions. Quantitative IVDr NMR serum spectroscopy is able to stratify PD patient samples of different etiology and can contribute to a wider understanding of the underlying metabolism-driven alterations e.g. in energy, amino acid, and lipoprotein metabolism. Though our overall cohort was large, major confounders such as age, sex and medication have a strong impact. That is why absolute quantification and detailed patient knowledge about metabolic confounders, is a premise for future translation of NMR serum spectroscopy to routine PD diagnostics.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Application of IVDr NMR spectroscopy to stratify Parkinson’s disease with absolute quantitation of blood serum metabolites and lipoproteins
- Date Crossref
- 22/05/2025
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Siemens (Germany) pays non établi dans la noticeEntreprise
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University of Tübingen Department of Preclinical Imaging and Radiopharmacy pays non établi dans la noticeUniversité ou école supérieure
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German Center for Neurodegenerative Diseases pays non établi dans la noticeStructure de recherche
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Hertie Institute for Clinical Brain Research pays non établi dans la noticeInstitution
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Bruker (United States) pays non établi dans la noticeEntreprise
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Ludwig-Maximilians-Universität München pays non établi dans la noticeUniversité ou école supérieure
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Charité - Universitätsmedizin Berlin pays non établi dans la noticeÉtablissement de santé
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TUM Klinikum pays non établi dans la noticeÉtablissement de santé
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Technical University of Munich pays non établi dans la noticeUniversité ou école supérieure
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University Hospital Magdeburg pays non établi dans la noticeÉtablissement de santé
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Otto-von-Guericke-Universität Magdeburg pays non établi dans la noticeUniversité ou école supérieure
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University of Göttingen pays non établi dans la noticeUniversité ou école supérieure
Siemens (Germany), Department of Preclinical Imaging and Radiopharmacy — University of Tübingen et German Center for Neurodegenerative Diseases, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.