The goal of this Phase I STTR proposal is to develop a new detection platform and methodology for early detection and characterization of Beta-amyloid peptide (AB), the primary protein component of senile plaques in Alzheimer's disease (AD). An extremely sensitive surface enhanced Raman spectroscopy product has been developed by Nanospectra Biosciences and its collaborators at Rice University that provides enhancements equal to or exceeding 10^10 uniformly across the substrate, enabling rapid quantification of picomolar levels of targets in fluids. This substrate is based on a new class of nanomaterials, called nanoshells, with extremely high near-field electromagnetic effects at their plasmon resonance peaks. Beta-amyloid peptide plays an important role in neurotoxicity and is a marker for AD progression. Evidence, both in our collaborator's (Dr. Good, UMBC) lab and others, indicates that we can develop a clustered sialic acid containing dendritic polymer that is a biological mimic of the cell surface and will have high affinity for disease specific conformations of AB. More specifically, we believe that we can exploit the relatively high affinity binding of sialic acid clusters to aggregated/fibril AB for the detection of soluble amyloid oligomers present in biological tissues such as cerebral spinal fluid or post mortem tissue samples using our unique surface-enhanced Raman spectroscopy platform.
The specific aims of this research include (1) development of the nanoshell surface sensor for detection; (2) synthesis of soluble clustered sialic acid dendrimers as mimics of ganglioside clusters on the membrane surface; and (3) development of detection methods that utilize the soluble clustered sialic acid dendrimers as a targeting agent for oligomeric/fibril AB.
| Patel, Dhara A; Henry, James E; Good, Theresa A (2007) Attenuation of beta-amyloid-induced toxicity by sialic-acid-conjugated dendrimers: role of sialic acid attachment. Brain Res 1161:95-105 |
