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Purification and characterization of brain clusterin
T Oda1, G M Pasinetti, H H Osterburg
1Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Biochemical and Biophysical Research Communications
|November 15, 1994
Summary
Clusterin protein levels are elevated in Alzheimer disease brains and may contribute to disease progression by inhibiting beta-amyloid aggregation and enhancing its toxicity.
Area of Science:
- Neuroscience
- Biochemistry
- Immunology
Background:
- Clusterin, also known as apolipoprotein J, is a glycoprotein found in various tissues.
- Elevated clusterin mRNA and protein in beta-amyloid deposits are observed in Alzheimer disease (AD).
Purpose of the Study:
- To characterize clusterin protein from human brain tissue.
- To investigate the functional roles of brain and serum clusterin in AD-related processes.
Main Methods:
- Quantification of clusterin protein in human AD and control brain extracts (cortex and hippocampus).
- Purification and comparison of brain and serum clusterin.
- Assays for complement-mediated hemolysis inhibition.
- Assessment of beta-amyloid (A beta) aggregation inhibition and cell toxicity (MTT assay) using PC12 cells.
Main Results:
- Clusterin protein was approximately 40% higher in AD brain extracts compared to controls.
- Human brain clusterin was slightly smaller than serum clusterin but functionally indistinguishable.
- Both brain and serum clusterin inhibited A beta aggregation and promoted oxidative stress in PC12 cells.
Conclusions:
- Clusterin is upregulated in Alzheimer disease brains.
- Clusterin's ability to inhibit A beta aggregation and enhance its toxicity suggests novel roles in AD pathogenesis.