2008 Grants - Gestwicki

Chemical Probes for Selective Recognition of Amyloid Oligomers

Jason E. Gestwicki, Ph.D.
University of Michigan
Ann Arbor, Michigan

2008 New Investigator Research Grant

Amyloid plaques, a characteristic pathologic feature of Alzheimer's disease, are formed from aggregates of the protein fragment beta-amyloid. However, the severity of Alzheimer's disease does not correlate well with the amount of amyloid plaque present. Instead, disease severity is more closely related to levels of beta-amyloid oligomers, which are much smaller aggregates of a few beta-amyloid molecules.

A primary goal of Alzheimer research is to develop diagnostic tools that can detect the disease in early stages, assess its progression and monitor response to treatment. Currently, imaging methods are being developed for this purpose, but most rely on detection of amyloid plaque using a chemical probe that binds to beta-amyloid and which can be detected by imaging.

Jason E. Gestwicki, Ph.D., and colleagues are studying chemical probes of beta-amyloid in an attempt to identify probes that can selectively identify beta-amyloid oligomers. They have developed a method for immobilizing aggregates of beta-amyloid at different stages of formation. They plan to test how different chemical probes bind to the various beta-amyloid aggregates using a technique called surface plasmon resonance.

When a suitable probe is identified, the researchers plan to develop the probe for use as an imaging agent. These studies may identify a probe that can reliably predict early steps in the development of Alzheimer's disease and be useful for diagnosis and disease-monitoring.