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Widespread alterations of alpha-synuclein in multiple system atrophy
1Department of Pathology, Mayo Clinic Jacksonville, Jacksonville, Florida, USA. dickson.dennis@mayo.edu
The American Journal of Pathology
|October 9, 1999
Summary
Multiple system atrophy (MSA) involves alpha-synuclein protein changes beyond visible brain lesions. These biochemical alterations may serve as a diagnostic signature for synucleinopathies like MSA.
Area of Science:
- Neuroscience
- Neuropathology
- Biochemistry
Background:
- Multiple system atrophy (MSA) is a rare neurodegenerative disorder characterized by glial cytoplasmic inclusions (GCI).
- GCIs are known to contain alpha-synuclein and are associated with autonomic dysfunction.
Purpose of the Study:
- To investigate the biochemical properties of alpha-synuclein in MSA.
- To correlate the amount of alpha-synuclein with the density of GCIs in different brain regions.
Main Methods:
- Immunohistochemistry was used to identify GCI markers in 21 MSA cases.
- Postmortem brain samples from 9 MSA cases were fractionated based on solubility.
- Alpha-synuclein levels were quantified using Western blots.
Main Results:
- GCIs were immunoreactive for alpha-synuclein and ubiquitin.
- Total alpha-synuclein was increased in MSA brains compared to controls, primarily in SDS-soluble fractions.
- SDS-soluble alpha-synuclein levels showed a poor correlation with GCI density.
Conclusions:
- Alpha-synuclein modifications in MSA are more widespread than indicated by GCI histopathology.
- Altered alpha-synuclein may represent a biochemical hallmark for synucleinopathies.