| Abstract
| - Small molecules that bind to aggregated forms of Aβpeptides show promise as potential in vivo labeling agentsfor the diagnosis and monitoring of Alzheimer's disease.A major challenge in developing potential imaging agentsthat target Aβ is to rapidly identify and evaluate theassociation of molecules with insoluble deposits of aggregated Aβ peptides. This paper describes a simple,parallel method to rapidly screen libraries of moleculesfor their ability to associate with fibrils formed fromsynthetic Aβ peptides by monitoring their ability to inhibitthe interaction of a monoclonal anti-Aβ IgG with thesefibrils. We demonstrate that this assay can detect theassociation of small molecules with Aβ fibrils at concentrations of small molecule in the nanomolar to millimolarrange. By comparing results from the screening of a smallset of 30 compounds, we illustrated that this assay canrapidly analyze the relative affinity of small molecules forAβ fibrils and identified eight compounds that can bindto Aβ fibrils at <20 μM concentrations. Significant advantages of this assay are (1) the ability to screenstructurally diverse molecules without requiring them tohave specific spectroscopic or radiolabeled properties, (2)the ability to estimate the percentage of the surface of thefibrils covered by the small molecules, and (3) the abilityto detect the association of small molecules that potentiallybind to different sites along the fibril axis. This assay alsohas minimal requirements for equipment or specializedfacilities and should, therefore, be useful for both academic and industrial laboratories.
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