Journal Article FZJ-2024-03584

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

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2024
Wiley New York, NY

Movement disorders 39(8), 1289-1299 () [10.1002/mds.29766]

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Abstract: BackgroundIdentifying 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.ObjectiveThe 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.MethodsIn 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.ResultsAll 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.ConclusionsWe 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.

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Contributing Institute(s):
  1. Kognitive Neurowissenschaften (INM-3)
Research Program(s):
  1. 5252 - Brain Dysfunction and Plasticity (POF4-525) (POF4-525)

Appears in the scientific report 2024
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Medline ; Creative Commons Attribution-NonCommercial-NoDerivs CC BY-NC-ND 4.0 ; OpenAccess ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Wiley ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; NationallizenzNationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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 Record created 2024-06-06, last modified 2025-02-04


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