TY  - JOUR
AU  - Kluge, Annika
AU  - Schaeffer, Eva
AU  - Bunk, Josina
AU  - Sommerauer, Michael
AU  - Röttgen, Sinah
AU  - Schulte, Claudia
AU  - Roeben, Benjamin
AU  - von Thaler, Anna-Katharina
AU  - Welzel, Julius
AU  - Lucius, Ralph
AU  - Heinzel, Sebastian
AU  - Xiang, Wei
AU  - Eschweiler, Gerhard W.
AU  - Maetzler, Walter
AU  - Suenkel, Ulrike
AU  - Berg, Daniela
TI  - Detecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease
JO  - Movement disorders
VL  - 39
IS  - 8
SN  - 0885-3185
CY  - New York, NY
PB  - Wiley
M1  - FZJ-2024-03584
SP  - 1289-1299
PY  - 2024
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - 38651526
UR  - <Go to ISI:>//WOS:001206343800001
DO  - DOI:10.1002/mds.29766
UR  - https://juser.fz-juelich.de/record/1027018
ER  -