2004 Investigator-Initiated Research Grant

Beta-amyloid is a tiny, sticky protein fragment that clumps together in stages, eventually forming structures called amyloid plaques. One of these stages may have toxic properties that harm cells, and much research is focused on how this damage happens. But other things besides beta-amyloid end up in plaques, and scientists have been taking them apart to determine what other relevant disease-related factors may be there.

One of these factors may be a certain “sugary molecular chain” that, according to some studies, helps beta-amyloid clusters arrange themselves into problematic forms. Other studies have shown that some parts of this chain, a smaller sugar molecule called glycosaminoglycan (GAG), may have some protective effect.

John M. Lee, M.D., Ph.D., and colleagues are investigating GAGs to address some of the apparent contradictions in findings so far. GAG molecules are not all the same size, and their differences may influence how they interact with other molecules. The researchers will test whether certain GAGs deter the longer sugary molecular chain and prevent the aggregation of beta-amyloid.

The investigators will administer varying doses of a GAG compound to genetically altered mice that develop an Alzheimer-like disorder and experience memory and learning deficits. They will determine if the treatment improves memory and learning behaviors in the mice and prevents the formation of beta-amyloid structures. The study may help demonstrate the validity of testing such a compound in clinical trials.