2004 New Investigator 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 clumps together in stages, eventually forming amyloid plaques. Recent studies have shown, however, that a tiny cluster of a few beta-amyloid molecules, called an oligomer—a very early stage in this clumping process—may be the primary toxic element in Alzheimer’s.

Other studies have shown that beta-amyloid is inclined to interact with zinc and copper ions, as well as certain lipids (fats) that are abundant in the membranes surrounding nerve cells and at important points of cell-to-cell communication. This interaction with metal ions and lipids is associated with a rapid formation of beta-amyloid oligomers.

Douglas V. Laurents, Ph.D., and his colleagues will use a technology called nuclear magnetic resonance to study the three-dimensional structure of beta-amyloid molecules and oligomers. They will investigate the structural factors of beta-amyloid that make it susceptible to metal and lipid interactions, determine how the structure of beta-amyloid changes when it interacts with these elements, and characterize how the structural properties of beta-amyloid oligomers may influence their function in the brain. This work may provide a more detailed understanding of beta-amyloid’s role in Alzheimer’s disease and contribute to the development of anti-amyloid therapies.