%0 Journal Article
%A Kluge, Annika
%A Schaeffer, Eva
%A Bunk, Josina
%A Sommerauer, Michael
%A Röttgen, Sinah
%A Schulte, Claudia
%A Roeben, Benjamin
%A von Thaler, Anna-Katharina
%A Welzel, Julius
%A Lucius, Ralph
%A Heinzel, Sebastian
%A Xiang, Wei
%A Eschweiler, Gerhard W.
%A Maetzler, Walter
%A Suenkel, Ulrike
%A Berg, Daniela
%T Detecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease
%J Movement disorders
%V 39
%N 8
%@ 0885-3185
%C New York, NY
%I Wiley
%M FZJ-2024-03584
%P 1289-1299
%D 2024
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ 38651526
%U <Go to ISI:>//WOS:001206343800001
%R 10.1002/mds.29766
%U https://juser.fz-juelich.de/record/1027018