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001027018 0247_ $$2datacite_doi$$a10.34734/FZJ-2024-03584
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001027018 1001_ $$00000-0001-7116-5484$$aKluge, Annika$$b0$$eCorresponding author
001027018 245__ $$aDetecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease
001027018 260__ $$aNew York, NY$$bWiley$$c2024
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001027018 520__ $$aBackgroundIdentifying individuals with Parkinson's disease (PD) already in the prodromal phase of the disease has become a priority objective for opening a window for early disease-modifying therapies.ObjectiveThe aim was to evaluate a blood-based α-synuclein seed amplification assay (α-syn SAA) as a novel biomarker for diagnosing PD in the prodromal phase.MethodsIn the TREND study (University of Tuebingen) biennial blood samples of n = 1201 individuals with/without increased risk for PD were taken prospectively over 4 to 10 years. We retrospectively analyzed blood samples of 12 participants later diagnosed with PD during the study to detect and amplify pathological α-syn conformers derived from neuronal extracellular vesicles using (1) immunoblot analyses with an antibody against these conformers and (2) an α-syn-SAA. Additionally, blood samples of n = 13 healthy individuals from the TREND cohort and n = 20 individuals with isolated rapid eye movement sleep behavior disorder (iRBD) from the University Hospital Cologne were analyzed.ResultsAll individuals with PD showed positive immunoblots and a positive α-syn SAA at the time of diagnosis. Moreover, all PD patients showed a positive α-syn SAA 1 to 10 years before clinical diagnosis. In the iRBD cohort, 30% showed a positive α-syn SAA. All healthy controls had a negative SAA.ConclusionsWe here demonstrate the possibility to detect and amplify pathological α-syn conformers in peripheral blood up to 10 years before the clinical diagnosis of PD in individuals with and without iRBD. The findings of this study indicate that this blood-based α-syn SAA assay has the potential to serve as a diagnostic biomarker for prodromal PD. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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001027018 7001_ $$00000-0002-0792-4383$$aSchaeffer, Eva$$b1
001027018 7001_ $$0P:(DE-HGF)0$$aBunk, Josina$$b2
001027018 7001_ $$0P:(DE-Juel1)179044$$aSommerauer, Michael$$b3$$ufzj
001027018 7001_ $$0P:(DE-Juel1)194632$$aRöttgen, Sinah$$b4$$ufzj
001027018 7001_ $$00000-0003-4006-1265$$aSchulte, Claudia$$b5
001027018 7001_ $$00000-0002-4905-8698$$aRoeben, Benjamin$$b6
001027018 7001_ $$0P:(DE-HGF)0$$avon Thaler, Anna-Katharina$$b7
001027018 7001_ $$0P:(DE-HGF)0$$aWelzel, Julius$$b8
001027018 7001_ $$0P:(DE-HGF)0$$aLucius, Ralph$$b9
001027018 7001_ $$0P:(DE-HGF)0$$aHeinzel, Sebastian$$b10
001027018 7001_ $$0P:(DE-HGF)0$$aXiang, Wei$$b11
001027018 7001_ $$0P:(DE-HGF)0$$aEschweiler, Gerhard W.$$b12
001027018 7001_ $$0P:(DE-HGF)0$$aMaetzler, Walter$$b13
001027018 7001_ $$0P:(DE-HGF)0$$aSuenkel, Ulrike$$b14
001027018 7001_ $$0P:(DE-HGF)0$$aBerg, Daniela$$b15
001027018 773__ $$0PERI:(DE-600)2041249-6$$a10.1002/mds.29766$$gp. mds.29766$$n8$$p1289-1299$$tMovement disorders$$v39$$x0885-3185$$y2024
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