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| Home > Publications Database > Detecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease |
| Home > Publications Database > Detecting Misfolded α‐Synuclein in Blood Years before the Diagnosis of Parkinson's Disease |
| Journal Article | DZNE-2024-00534 |
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2024
Wiley
New York, NY
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Please use a persistent id in citations: doi:10.1002/mds.29766
Abstract: Identifying 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.The 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.In 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.All 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.We 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.
Keyword(s): Humans (MeSH) ; Parkinson Disease: blood (MeSH) ; Parkinson Disease: diagnosis (MeSH) ; alpha-Synuclein: blood (MeSH) ; Female (MeSH) ; Male (MeSH) ; Aged (MeSH) ; Middle Aged (MeSH) ; Prodromal Symptoms (MeSH) ; Biomarkers: blood (MeSH) ; REM Sleep Behavior Disorder: blood (MeSH) ; REM Sleep Behavior Disorder: diagnosis (MeSH) ; Retrospective Studies (MeSH)
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