Attenuation of beta-amyloid induced toxicity by sialic acid-conjugated dendrimeric polymers

beta-amyloid (Abeta) is the primary protein component of senile plaques in Alzheimer's disease and is believed to be associated with neurotoxicity in the disease. We and others have shown that Abeta binds with relatively high affinity to clustered sialic acid residues on cell surfaces and that removal of cell surface sialic acids attenuate Abeta toxicity. In the current work, we have prepared sialic acid conjugated dendrimeric polymers and assessed the ability of these sialic acid conjugated dendrimers to prevent Abeta toxicity. Flow cytometry was used to analyze viability of SH-SY5Y neuroblastoma cells and the effects of soluble and clustered sialic acid mimics on Abeta cell toxicity. Soluble sialic acid attenuation of Abeta induced toxicity was effective only at high sialic acid concentrations and low Abeta concentration. The sialic acid conjugated dendrimeric polymers were able to attenuate Abeta toxicity at micromolar concentrations, or approximately three orders of magnitude lower concentrations than the soluble sialic acid. The toxicity prevention properties of the sialic acid modified dendrimers were a function of dendrimer size. This work may lead to the development of new classes of therapeutics for the prevention of Abeta toxicity.