Surface Plasmon Resonance Assay for Identification of Small Molecules Capable of Inhibiting Aβ Aggregation

Toxic aggregates of amyloid-beta (Aβ) have importance in the pathology of Alzheimer's disease, and inhibition of aggregate formation is considered to be a promising strategy for drug development. Here, we report a simple and rapid surface plasmon resonance (SPR) assay method that can identify potential Aβ aggregation inhibitors. Our assay is based on the SPR shifting of the Aβ-gold nanoparticle (Aβ-GNP) aggregates by size under the influence of an Aβ aggregation inhibitor. This user-friendly assay features a short assay time with a low reagent consumption that can be easily adapted as a high-throughput screen. We demonstrated that an effective Aβ aggregation inhibitor induces the blue-shifted SPR peaks of the Aβ-GNP aggregates by hindering the formation of long fibrillar aggregates. Moreover, the blue shifting was correlated to the efficacy and concentrations of an Aβ aggregation inhibitor. Overall, our findings suggest that our simple SPR assay can be a powerful tool to screen small molecules targeting Aβ aggregation.