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

Jenny Hällqvist (), Michael Bartl (), Mohammed Dakna, Sebastian Schade, Paolo Garagnani, Maria-Giulia Bacalini, Chiara Pirazzini, Kailash Bhatia, Sebastian Schreglmann, Mary Xylaki, Sandrina Weber, Marielle Ernst, Maria-Lucia Muntean, Friederike Sixel-Döring, Claudio Franceschi, Ivan Doykov, Justyna Śpiewak, Héloїse Vinette, Claudia Trenkwalder, Wendy E. Heywood, Kevin Mills and Brit Mollenhauer
Additional contact information
Jenny Hällqvist: UCL Institute of Child Health and Great Ormond Street Hospital
Michael Bartl: University Medical Center Goettingen
Mohammed Dakna: University Medical Center Goettingen
Sebastian Schade: Paracelsus-Elena-Klinik
Paolo Garagnani: University of Bologna
Maria-Giulia Bacalini: IRCCS Istituto delle Scienze Neurologiche di Bologna
Chiara Pirazzini: University of Bologna
Kailash Bhatia: Queen Square
Sebastian Schreglmann: Queen Square
Mary Xylaki: University Medical Center Goettingen
Sandrina Weber: University Medical Center Goettingen
Marielle Ernst: University Medical Center Goettingen
Maria-Lucia Muntean: Paracelsus-Elena-Klinik
Friederike Sixel-Döring: Paracelsus-Elena-Klinik
Claudio Franceschi: University of Bologna
Ivan Doykov: UCL Institute of Child Health and Great Ormond Street Hospital
Justyna Śpiewak: UCL Institute of Child Health and Great Ormond Street Hospital
Héloїse Vinette: UCL Institute of Child Health and Great Ormond Street Hospital
Claudia Trenkwalder: Paracelsus-Elena-Klinik
Wendy E. Heywood: UCL Institute of Child Health and Great Ormond Street Hospital
Kevin Mills: Clinical and Movement Neurosciences
Brit Mollenhauer: University Medical Center Goettingen

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract 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.

Date: 2024
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DOI: 10.1038/s41467-024-48961-3

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