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2005 Grant - Zhou
Mevalonate Biosynthetic Pathway in APP Processing
Yan Zhou, Ph.D.
Medical University of South Carolina
Charleston, South Carolina
2005 New Investigator Research Grant
Some studies have revealed that people taking cholesterol-lowering drugs called statins have a much lower risk of developing Alzheimer's disease. In addition to reducing blood cholesterol levels, statins have been shown to decrease the production of other lipids (fats) such as geranylgeranyl pyrophosphate (GGPP).
Studies have shown that this lipid may increase the generation of beta-amyloid, a sticky protein fragment generated from the larger amyloid precursor protein (APP). Beta-amyloid is suspected of disrupting communi-cation between neurons in the brains of people with Alzheimer's disease. This finding suggests that statins may reduce the risk of Alzheimer's not because of its cholesterol-lowering effect but because of its GGPP-lowering effect.
Using cultured cells and genetically altered mice, Yan Zhou, Ph.D., and colleagues will test this hypothesis. The scientists will determine if GGPP can elevate production of beta-amyloid by increasing the activity of a gamma-secretase, a cluster of enzymes involved in production of beta-amyloid. The researchers will examine the mice to determine if GGPP causes more deposits of beta-amyloid to form in the brain.
This research may provide important insight into the effects of statin treatment on Alzheimer's disease pathology, identify contributing factors to Alzheimer pathology and lead to new therapies specifically targeted to these factors.