Vernon M. Ingram, Ph.D., D.Sc.
Massachusetts Institute of Technology
Cambridge, Massachusetts

2004 Investigator-Initiated Research Grant

Beta-amyloid is a protein fragment, or peptide, 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, and some of these stages have properties that may make them toxic to cells.

A large effort is under way to develop drugs that target beta-amyloid. Some strategies involve blocking its production, and other experimental drugs are intended to clear it from the brain. Vernon Ingram, Ph.D., Sc.D., and colleagues are investigating strategies for preventing beta-amyloid from clumping together into its suspect toxic form.

One approach the investigators are using is the identification of “decoy peptides.” These very tiny peptides function as decoys because they have features that make them “attractive” to beta-amyloid peptides, which may bind to the decoys rather than to each other. The researchers are also identifying chemical compounds that interfere with beta-amyloid clumping. Both of these approaches should, in theory, prevent the formation of toxic beta-amyloid structures.

The current study is an effort to expand the candidate pool of decoy peptides and compounds, characterize the features of each candidate, and select the best candidates for testing in mice that are genetically altered to develop an Alzheimer-like disorder. The outcome of this work may demonstrate the potential of this therapeutic strategy and advance efforts to create disease-modifying drugs.