Plasma proteomics identify biomarkers predicting Parkinson’s disease up to 7 years before symptom onset

Parkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the disabling motor stage. We need objective biomarkers for early/pre-motor disease stages to be able to intervene and slow the underlying...

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Veröffentlicht in:Nature communications Jg. 15; H. 1; S. 4759 - 18
Hauptverfasser: Hällqvist, Jenny, Bartl, Michael, Dakna, Mohammed, Schade, Sebastian, Garagnani, Paolo, Bacalini, Maria-Giulia, Pirazzini, Chiara, Bhatia, Kailash, Schreglmann, Sebastian, Xylaki, Mary, Weber, Sandrina, Ernst, Marielle, Muntean, Maria-Lucia, Sixel-Döring, Friederike, Franceschi, Claudio, Doykov, Ivan, Śpiewak, Justyna, Vinette, Héloїse, Trenkwalder, Claudia, Heywood, Wendy E., Mills, Kevin, Mollenhauer, Brit
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 18.06.2024
Nature Publishing Group
Nature Portfolio
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Aged
Biomarkers
Biomarkers - blood
Blood
Case-Control Studies
Clinical trials
Complement component C3
Female
Granulin
Humanities and Social Sciences
Humans
Inhibitors
Machine Learning
Male
Mannan
Mass Spectrometry
Mass spectroscopy
Middle Aged
multidisciplinary
Neurodegenerative diseases
Parkinson Disease - blood
Parkinson Disease - diagnosis
Parkinson's disease
Proteinase inhibitors
Proteomics
Proteomics - methods
REM sleep
REM Sleep Behavior Disorder - blood
REM Sleep Behavior Disorder - diagnosis
Science
Science (multidisciplinary)
Signal transduction
Signs and symptoms
Sleep
Sleep disorders
Wnt protein
ISSN:2041-1723, 2041-1723
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Zusammenfassung:Parkinson’s disease is increasingly prevalent. It progresses from the pre-motor stage (characterised by non-motor symptoms like REM sleep behaviour disorder), to the disabling motor stage. We need objective biomarkers for early/pre-motor disease stages to be able to intervene and slow the underlying neurodegenerative process. Here, we validate a targeted multiplexed mass spectrometry assay for blood samples from recently diagnosed motor Parkinson’s patients ( n  = 99), pre-motor individuals with isolated REM sleep behaviour disorder (two cohorts: n  = 18 and n  = 54 longitudinally), and healthy controls ( n  = 36). Our machine-learning model accurately identifies all Parkinson patients and classifies 79% of the pre-motor individuals up to 7 years before motor onset by analysing the expression of eight proteins—Granulin precursor, Mannan-binding-lectin-serine-peptidase-2, Endoplasmatic-reticulum-chaperone-BiP, Prostaglaindin-H2-D-isomaerase, Interceullular-adhesion-molecule-1, Complement C3, Dickkopf-WNT-signalling pathway-inhibitor-3, and Plasma-protease-C1-inhibitor. Many of these biomarkers correlate with symptom severity. This specific blood panel indicates molecular events in early stages and could help identify at-risk participants for clinical trials aimed at slowing/preventing motor Parkinson’s disease. Parkinson’s disease is lacking easily accessible biomarkers. Here the authors show, that targeted blood proteomics is feasible to identify the patients and to predict the phenoconvertion in prodromal subjects up to 7 years before symptom onset.
Bibliographie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-024-48961-3