Surface plasmon resonance biosensors for simultaneous monitoring of amyloid-beta oligomers and fibrils and screening of select modulators

Oligomeric amyloid-beta (A beta) peptides are considered as the most toxic species in Alzheimer's disease (AD). Monitoring of the A beta aggregation profiles is critical for elucidating the oligomer toxicity and may serve as a therapeutic target for AD. By immobilizing the capture antibodies of A11 and OC that are specific to the oligomers and fibrils, respectively, in separate fluidic channels, a novel surface plasmon resonance (SPR) biosensor was designed for monitoring the oligomeric and fibrillar species of A beta(1-42) simultaneously. The influence of curcumin, Cu2+ and methylene blue on the amount of toxic oligomers and fibrils was evaluated. The half maximal inhibitory concentration (IC50) of curcumin and methylene blue was determined. The formation of A beta fibrils was also validated by the thioflavin T (ThT) fluorescence assay. The results demonstrate the utility of SPR as an analytical tool for rapid and comprehensive monitoring of A beta aggregation and screening of Aa modulators.