Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease

Kluge A, Schaeffer E, Bunk J, Sommerauer M, Röttgen S, Schulte C, Roeben B, von Thaler AK, Welzel J, Lucius R, Heinzel S, Xiang W, Eschweiler GW, Maetzler W, Suenkel U, Berg D (2024)

Publication Type: Journal article

Publication year: 2024

Journal

Movement Disorders Wiley-Blackwell

DOI: 10.1002/mds.29766

Abstract

Background: Identifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies. Objective: The aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase. Methods: In the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α-syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α-syn-SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed. Results: All individuals with PD showed positive immunoblots and a positive α-syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA. Conclusions: We here demonstrate the possibility to detect and amplify pathological α-syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Authors with CRIS profile

Wei Xiang Department of Molecular Neurology

Involved external institutions

Universitätsklinikum Schleswig-Holstein (UKSH) DE Germany (DE) Hertie-Institut für klinische Hirnforschung DE Germany (DE) Universitätsklinikum Köln DE Germany (DE) Christian-Albrechts-Universität zu Kiel DE Germany (DE) Universitätsklinikum Tübingen DE Germany (DE)

How to cite

APA:

Kluge, A., Schaeffer, E., Bunk, J., Sommerauer, M., Röttgen, S., Schulte, C.,... Berg, D. (2024). Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease. Movement Disorders. https://doi.org/10.1002/mds.29766

MLA:

Kluge, Annika, et al. "Detecting Misfolded α-Synuclein in Blood Years before the Diagnosis of Parkinson's Disease." Movement Disorders (2024).

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