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alpha- and beta-secretase: profound changes in Alzheimer's disease
Susan J Tyler1, David Dawbarn, Gordon K Wilcock
1Molecular Neurobiology Unit, URCN (Care of the Elderly) University of Bristol, Bristol Royal Infirmary, Bristol, UK.
Biochemical and Biophysical Research Communications
|November 26, 2002
Summary
Alzheimer
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Alzheimer's disease is characterized by amyloid plaques, formed by beta-amyloid (Abeta) peptide.
- Amyloid Precursor Protein (APP) processing by alpha-secretase normally prevents Abeta formation.
- Beta-secretase activity increases Abeta production.
Purpose of the Study:
- To investigate the activity levels of alpha-secretase and beta-secretase in Alzheimer's disease.
- To determine the role of secretase activity in the pathogenesis of sporadic Alzheimer's disease.
Main Methods:
- Enzyme activity assays were performed on temporal cortex samples from Alzheimer's disease patients and normal controls.
- Quantification of alpha-secretase and beta-secretase activity.
Main Results:
- A significant decrease in alpha-secretase activity (81% of normal) was observed in Alzheimer's disease brains.
- A substantial increase in beta-secretase activity (185% of normal) was found in Alzheimer's disease brains.
- Eighty percent of Alzheimer's disease cases showed either increased beta-secretase, decreased alpha-secretase, or both.
Conclusions:
- The imbalance between decreased alpha-secretase and increased beta-secretase activity contributes to Abeta deposition in Alzheimer's disease.
- This enzymatic dysregulation may explain the common development of Alzheimer's disease.
- Targeting secretase pathways could be a therapeutic strategy for Alzheimer's disease.