Objective: To identify seeding capacities of soluble α-synuclein (α-syn) conformers derived from neuronal extracellular vesicles (NEs) from Parkinson´s disease (PD) patients with different disease durations (1 to more than 15 years).
Background: The synaptic protein α-syn is able to form toxic oligomers as well as insoluble amyloid fibrils and can be transmitted from cell to cell. It is known that pathological protein conformers can induce physiological monomeric conformers to form also pathological structures (α-syn seed amplification). In a recent study we were able to detect seeding of soluble α-syn derived from PD-NEs with a sensitivity of 100 %. However, so far it remains unclear how α-syn seeding capacity changes during the natural course of PD.
Method: We studied 80 PD patients recruited in the outpatient clinical of the Department of Neurology in Tübingen between 2008 and 2022 and 20 age- and gender matched healthy controls. Individuals were selected based on their disease duration, with the year of diagnosis defined as starting point, and divided into four groups (disease duration 1 to 4 years; 5 to 9 years; 10 to 14 years; more than 15 years). After isolation of NEs from blood plasma of 80 PD patients and control individuals, we analyzed the seeding capacities of the NE-derived α-syn conformers.
Results: All except one individual with PD showed increased fluorescence (Thioflavin T, ThT intensity) signals in the seed amplification assay (SAA). In the control cohort no seeding capacity was measured. Dividing individuals with PD into four different categories of disease duration, our data demonstrate that patients with longer disease duration showed significant less ThT signals as marker for α-syn aggregation (p<0.001).
Conclusion: This study confirms a very high sensitivity of this blood-based α-syn biomarker. Moreover, we could demonstrate that PD-NE-derived α-syn seeding decreases with disease duration and can be detected up to 23 years after diagnosis.
To cite this abstract in AMA style:
A. Kluge, E. Schaeffer, K. Brockmann, C. Schulte, C. Deuschle, J. Bunk, W. Maetzler, D. Berg. Blood derived α-synuclein seeding in the course of Parkinson’s Disease [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/blood-derived-%ce%b1-synuclein-seeding-in-the-course-of-parkinsons-disease/. Accessed June 14, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/blood-derived-%ce%b1-synuclein-seeding-in-the-course-of-parkinsons-disease/