Lee-Way Jin, M.D., Ph.D.
University of California at Davis
Sacramento, California

2006 Investigator-Initiated Research Grant

The beta-amyloid protein fragment is a key suspect in Alzheimer pathology. Beta-amyloid molecules are chemically sticky and have a propensity to aggregate, or assemble themselves into larger and larger structures, eventually forming amyloid plaques. Recent studies have shown that small beta-amyloid aggregates, called oligomers, may be the primary toxic agents in Alzheimer's disease, and researchers have been looking for means to inhibit the formation of oligomers.

In previous research, scientists developed a number of small molecules for use as probes to label amyloid plaques in people with Alzheimer's disease. The molecular probes have certain characteristics essential for an Alzheimer drug. They can get past the brain's defense mechanism, they bind to beta-amyloid aggregates, and they don't bind to other molecules in the brain.

Lee-Way Jin, M.D., Ph.D., and colleagues have determined that some of these small molecules may also disrupt beta-amyloid oligomers and may protect cells from beta-amyloid-induced toxicity. In this study, the investigators will examine two of the drug-like molecules, characterize their interaction with beta-amyloid in cell cultures and test their therapeutic effect in genetically altered mice that develop an Alzheimer-like disorder. This work may provide evidence for future investigations in clinical studies.