(259c) Developing Biomimetic Sialic Acid Polymers to Prevent Beta Amyloid Cell Interactions

Alzheimer's disease is a progressive and fatal brain disease that currently affects over 5 million Americans and accounts for approximately 60% of dementia cases. It is believed that beta-amyloid peptide (Aβ), the primary protein component in senile plaques, is toxic to neurons when aggregated and is a major causative factor in neurodegeneration associated with Alzheimer's. Evidence suggests that Aβ binds to neurons via sialic acids. The goal of this research is to create novel Sialic Acid Polymers (SAPs) that have the potential to cross the blood brain barrier, are non-toxic, and have controllable valency and architecture that can mimic the cell surface, and thus will compete with the cell surface for Aβ binding. We have developed a novel polymer that is synthesized via a free radical polymerization of an alkene-epoxide derivatized sialic acid. We examined the effect of polymerization conditions on the molecular weight of polymer using viscosity measurements. We then examined the intrinsic toxicity of polymers on cultured SH-SY5Y cells, a neuroblastoma cell line used to model neuron properties. We also examined the ability of polymers of different molecular weights to prevent Aβ binding to cells. We investigated the polymer's ability to partition into both aqueous and organic phases, as a measure of the polymer's ability to cross the blood brain barrier in vivo. Finally we determined the relationship between polymer molecular weight, polymer concentration, and ability of polymer to attenuate beta amyloid toxicity. We believe that this work represents the first report of a sialic acid polymer via this route, with properties tailored for applications in Aβ toxicity attenuation associated with Alzheimer's disease.