Morphology Specific Antibodies to Beta-Amyloid

Project Summary

Alzheimer's Disease (AD) is characterized by the presence of neuritic plaques and neurofibrillary tangles. The role of Aß in AD is still controversial, an issue that has been complicated greatly by the multiple lengths and morphologies of Aß. A wealth of literature suggests the various lengths and morphologies have different effects on neuron viability and memory. In order to reliably assess the roles of Aß and anti-Aß vaccination strategies in AD, highly specific and very well-defined reagents such as single chain antibody binding variable domains (scFvs) that target individual Aß forms and morphologies are needed. Using a novel technology combining antibody diversity and microscopic imaging techniques, scFvs against specific Aß morphologies can be isolated. The isolated scFvs can be affinity matured to have extremely high specificity for the target ligands. The hypothesis of this proposal is that highly specific and well defined scFvs to specific oligomeric morphologies of Aß can be isolated by useful therapeutics for treating AD. The long term goal is to use the pool of morphology specific scFvs to probe the roles of the various Aß morphologies in AD and to test the value of these scFvs as potential diagnostic and therapeutic agents.