Related Experiment Video
Updated: Aug 16, 2026
09:27
Sequential Extraction of Soluble and Insoluble Alpha-Synuclein from Parkinsonian Brains
Published on: January 5, 2016
α-Synuclein strain homogeneity in multiple system atrophy subtypes
Heather H C Lau1,2, Nicholas R G Silver1,2, Surabhi Mehra1
1Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada.
Brain Pathology (Zurich, Switzerland)
|August 15, 2026
Summary
Distinct alpha-synuclein strains do not explain multiple system atrophy (MSA) subtypes. Instead, the same alpha-synuclein strain forming in different brain regions likely causes varied disease presentations in MSA-C and MSA-P.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Synucleinopathies, including multiple system atrophy (MSA), exhibit clinical and pathological diversity.
- This diversity is hypothesized to stem from conformationally distinct alpha-synuclein aggregate strains.
- MSA presents as two subtypes: MSA-C (cerebellar) and MSA-P (parkinsonian), differing in clinical and neuropathological features.
Purpose of the Study:
- To investigate whether distinct alpha-synuclein strains are present in MSA-C versus MSA-P.
- To compare the conformational and seeding properties of alpha-synuclein aggregates from MSA subtypes.
- To assess the impact of MSA-C and MSA-P derived aggregates on disease progression in a mouse model.
Main Methods:
- Biochemical fingerprinting (limited proteolysis, conformational stability assays) of alpha-synuclein aggregates from human MSA-C and MSA-P brain tissue.
- Propagation studies in M83 transgenic mice inoculated with aggregates from MSA subtypes.
- Seed amplification assays to evaluate the seeding properties of aggregates.
- Monitoring disease kinetics and alpha-synuclein deposition in inoculated mice.
Main Results:
- Biochemical analyses revealed no conformational differences between alpha-synuclein aggregates from MSA-C and MSA-P, even after in vivo propagation.
- Seed amplification assays showed indistinguishable seeding attributes for aggregates from both MSA subtypes.
- M83 mice inoculated with MSA-C or MSA-P aggregates exhibited similar disease progression rates and levels of alpha-synuclein deposition.
Conclusions:
- The findings suggest that distinct alpha-synuclein strains are unlikely to be the cause of MSA subtypes (MSA-C and MSA-P).
- A revised model proposes that the same alpha-synuclein strain initiates aggregation in different brain regions, leading to varied disease manifestations.
- This challenges the strain-based hypothesis for MSA heterogeneity and points towards regional seeding as a key factor.
Keywords:
multiple system atrophypropagationseed amplification assaystrainssubtypestransgenic miceα‐synucleinMore Related Videos
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