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2013 Grants - Fryer
The Role of CLU and LCN2 in Alzheimer's Disease and Normal Cognitive Function
John David Fryer, Ph.D.
Mayo Clinic Jacksonville
2013 New Investigator Research Grant
Clusterin (CLU) is a protein found in many tissues and has been linked with many functions in the brain and other parts of the body. Clusterin also binds beta-amyloid, a protein fragment implicated in the molecular mechanisms of Alzheimer's disease. Furthermore, recent studies have found evidence that some forms of clusterin increase the risk for Alzheimer's disease compared to other forms.
John David Fryer, Ph.D., and colleagues have proposed a series of experiments to study the function of clusterin and its possible role in Alzheimer's disease. They will also study a related protein, lipocalin-2 (LCN2), which is increased alongside clusterin in parts of the brain affected by amyloid plaques (one of the characteristic brain changes associated with Alzheimer's disease).
Using molecular techniques, the researcher will create mice lacking either the clusterin or lipocalin-2 gene to study how removal of these proteins affects brain function. Dr. Fryer and colleagues will study how loss of clusterin or lipocalin-2 affects the development of disease in Alzheimer's-like mice, including the development of amyloid plaques, as well as effects on learning and memory. Finally, Dr. Fryer's team will create strains of mice in which the amount of clusterin in the brain can be controlled by drug treatment. These studies will yield valuable new clues about the role of clusterin in amyloid plaque formation, and they may aid in the identification of new targets for drug treatment to prevent or slow the progression of Alzheimer's disease.