Yoshitaka Ishii, Ph.D.
University of Illinois
Chicago, Illinois

2003 New Investigator Research Grant

The beta-amyloid protein fragment accumulates in stages to form plaques in Alzheimer’s disease. These somewhat distinct stages may have different levels of toxicity and may interact in different ways with cells. An understanding of the atomic structure of these stages may provide clues about how beta-amyloid accumulates and how the various stages affect brain cells. This kind of structural investigation is difficult, however, because the early stages are soluble and do not lend themselves well to standard methods of structural analysis.

This research group recently demonstrated the adaptation of a current method of structural analysis to investigate these soluble stages of amyloid accumulation. The scientists will apply this method and other biochemical analyses to construct three-dimensional “models” of the tiny clusters called protofibrils and fibrils. They will investigate how the process of beta-amyloid accumulation is linked to atomic-level changes in these structures. The outcome of this work may provide a kind of structural map of amyloid accumulation and a foundation for other efforts to understand the role of beta-amyloid in Alzheimer pathology and to inhibit the disease process.