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| 001 | 1027018 | ||
| 005 | 20250204113900.0 | ||
| 024 | 7 | _ | |a 10.1002/mds.29766 |2 doi |
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| 100 | 1 | _ | |a Kluge, Annika |0 0000-0001-7116-5484 |b 0 |e Corresponding author |
| 245 | _ | _ | |a Detecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease |
| 260 | _ | _ | |a New York, NY |c 2024 |b Wiley |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a 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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