Application of IVDr NMR spectroscopy to stratify Parkinson’s disease with absolute quantitation of blood serum metabolites and lipoproteins

被引：0

作者：

Georgy Berezhnoy ^{[1
]}

Gyuntae Bae ^{[1
]}

Leonie Wüst ^{[1
]}

Claudia Schulte ^{[2
]}

Claire Cannet ^{[3
]}

Isabel Wurster ^{[4
]}

Milan Zimmermann ^{[2
]}

Alexander Jäck ^{[3
]}

Eike Jakob Spruth ^{[2
]}

Julian Hellmann-Regen ^{[5
]}

Sandra Roeske ^{[6
]}

Dominik Pürner ^{[7
]}

Wenzel Glanz ^{[8
]}

Fabian Maass ^{[7
]}

Felix Hufschmidt ^{[9
]}

Ingo Kilimann ^{[10
]}

Elisabeth Dinter ^{[11
]}

Okka Kimmich ^{[12
]}

Anna Gamez ^{[13
]}

Johannes Levin ^{[14
]}

Josef Priller ^{[15
]}

Oliver Peters ^{[16
]}

Michael Wagner ^{[11
]}

Alexander Storch ^{[17
]}

Paul Lingor ^{[18
]}

Emrah Düzel ^{[19
]}

Christoph van Riesen ^{[20
]}

Ullrich Wüllner ^{[21
]}

Stefan Teipel ^{[11
]}

Björn Falkenburger ^{[22
]}

Mathias Bähr ^{[11
]}

Inga Zerr ^{[5
]}

Gabor C. Petzold ^{[6
]}

Annika Spottke ^{[23
]}

Patricia Rizzu ^{[7
]}

Frederic Brosseron ^{[8
]}

Hartmut Schäfer ^{[24
]}

Thomas Gasser ^{[25
]}

Christoph Trautwein ^{[7
]}

机构：

[1] University of Tübingen,Werner Siemens Imaging Center, Department of Preclinical Imaging and Radiopharmacy

[2] University of Tübingen,Hertie Institute for Clinical Brain Research, Department of Neurodegenerative Diseases

[3] German Center for Neurodegenerative Diseases (DZNE),Department of Neurology

[4] Bruker BioSpin GmbH & Co. KG (AIC Division),Neuropsychiatry and Laboratory of Molecular Psychiatry, Department of Psychiatry and Psychotherapy

[5] German Center for Neurodegenerative Diseases (DZNE),Department of Psychiatry and Neurosciences

[6] University Hospital of Munich,ECRC Experimental and Clinical Research Center

[7] Ludwig-Maximilians-Universität (LMU) Munich,Department of Neurology, School of Medicine, University Hospital München rechts der Isar

[8] German Center for Neurodegenerative Diseases (DZNE),Institute of Cognitive Neurology and Dementia Research

[9] Charité - Universitätsmedizin Berlin,Clinic for Neurology, Medical Faculty

[10] Charité Universitätsmedizin Berlin,Department of Neurology

[11] Charité – Universitätsmedizin Berlin,Department of Old Age Psychiatry and Cognitive Disorders

[12] German Center for Neurodegenerative Diseases (DZNE),Department of Psychosomatic Medicine

[13] Technical University of Munich,Department of Neurology

[14] German Center for Neurodegenerative Diseases (DZNE),Department of Vascular Neurology

[15] Otto-von-Guericke University,Department of Psychiatry and Psychotherapy, School of Medicine and Health

[16] University Hospital Magdeburg,Department of Neurology

[17] University Medical Center,Institute of Cognitive Neuroscience

[18] Georg August University,Department of Neurology

[19] University Hospital Bonn and University of Bonn,M3 Research Center for Malignome, Metabolome and Microbiome, Medical Faculty

[20] German Center for Neurodegenerative Diseases (DZNE),Core Facility Metabolomics, Medical Faculty

[21] Rostock University Medical Center,undefined

[22] German Center for Neurodegenerative Diseases (DZNE),undefined

[23] University Hospital Carl Gustav Carus,undefined

[24] Technische Universität Dresden,undefined

[25] University Hospital Bonn,undefined

[26] Munich Cluster for Systems Neurology (SyNergy) Munich,undefined

[27] Technical University of Munich,undefined

[28] German Center for Mental Health (DZPG),undefined

[29] University of Edinburgh and UK DRI,undefined

[30] Charité – Universitätsmedizin Berlin,undefined

[31] corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin-Institute of Psychiatry and Psychotherapy,undefined

[32] University Medical Centre,undefined

[33] University College London,undefined

[34] German Center for Neurodegenerative Diseases (DZNE),undefined

[35] University of Bonn,undefined

[36] University of Tübingen,undefined

[37] University of Tübingen,undefined

来源：

Scientific Reports | / 15卷 / 1期

关键词：

Parkinson’s disease; Recessive inheritance; Blood; Dementia; Biomarkers;

D O I：

10.1038/s41598-025-01352-0

中图分类号：

学科分类号：

摘要：

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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