Susan W. Liebman, Ph.D.
University of Illinois
Chicago, Illinois

2006 Investigator-Initiated Research Grant

Beta-amyloid is a protein fragment that may be a key factor in damaging cell-to-cell communication and causing the loss of brain cells in Alzheimer's disease. Beta-amyloid molecules assemble themselves into small aggregates, which, in turn, form larger and larger aggregates, eventually forming amyloid plaque. Recent research has indicated that very small aggregates of beta-amyloid-some of the earliest stages of aggregation-may prove to be the main toxic factor in Alzheimer's.

Susan W. Liebman, Ph.D., and colleagues will use genetically altered yeast to study small beta-amyloid aggregates. In these cells, the researchers have fused beta-amyloid to a yeast protein called a reporter protein. If beta-amyloid molecules do not form aggregates, the reporter protein is fully active, enabling the yeast cells to grow and multiply. If beta-amyloid molecules aggregate, the reporter protein is not fully active, resulting in stunted cell growth.

The researchers will use this yeast model to screen a large number of small molecules that may be able to block beta-amyloid aggregation. Cell growth will indicate that a test molecule is blocking aggregation; stunted growth will indicate that the test molecule is not working. This strategy should enable the investigators to identify candidate molecules that can be studied further as potential disease-modifying treatments of Alzheimer's disease.