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Updated: Jan 28, 2026
09:44
Generation of Alpha-Synuclein Preformed Fibrils from Monomers and Use In Vivo
Published on: June 2, 2019
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Seeding variability of different alpha synuclein strains in synucleinopathies
Niccolò Candelise1, Matthias Schmitz1, Franc Llorens2
1Department of Neurology, University Medicine Goettingen and the German Center for Neurodegenerative Diseases (DZNE), Göttingen, Germany.
Annals of Neurology
|February 27, 2019
Summary
Distinct alpha-synuclein strains in dementia with Lewy bodies (DLB) and Parkinson's disease (PD) were identified using RT-QuIC. These findings explain disease variability and may lead to specific diagnostics and therapies for alpha-synucleinopathies.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Alpha-synucleinopathies like DLB and PD present with variable pathologies and clinical phenotypes.
- The underlying reasons for this heterogeneity are not fully understood.
- Distinct alpha-synuclein conformers, or strains, are hypothesized to contribute to disease variability.
Purpose of the Study:
- To analyze the seeding activity of alpha-synuclein seeds from DLB and PD brains using RT-QuIC.
- To investigate the structural and morphological characteristics of alpha-synuclein aggregates produced by RT-QuIC.
- To differentiate between alpha-synuclein strains in DLB and PD.
Main Methods:
- Brain-derived alpha-synuclein seeds from DLB, PD, and control cases were analyzed via RT-QuIC.
- RT-QuIC products underwent biochemical and morphological characterization using Western blot, Raman spectroscopy, AFM, and TEM.
- Seeding activity and aggregation kinetics were compared across disease groups.
Main Results:
- DLB-derived seeds exhibited distinct seeding kinetics in RT-QuIC compared to PD and control seeds.
- RT-QuIC reactions seeded with DLB material generated proteinase K-resistant, fibrillary alpha-synuclein.
- PD and control seeds did not efficiently convert wild-type alpha-synuclein substrate in the RT-QuIC assay.
Conclusions:
- Structural variations in alpha-synuclein seeds demonstrate the existence of distinct alpha-synuclein strains in DLB and PD.
- This study provides evidence for different alpha-synuclein strains contributing to the clinical heterogeneity of alpha-synucleinopathies.
- Findings offer potential for developing strain-specific diagnostic tools and targeted therapeutic strategies for DLB and PD.
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