Cross-Reactive Fluorescent Sensor Array for Discrimination of Amyloid Beta Aggregates

Abstract

It has been hypothesized that misfolding and misassembly of proteins into various aggregation states contribute to several neurodegenerative diseases. For instance, amyloid beta (Aβ) aggregation is considered a major factor in Alzheimer's disease pathogenesis. Herein, a fluorescent sensor array for detecting Aβ aggregates was fabricated using two probe pairs of conjugated polyelectrolytes and organic dye molecules, PPE1-Thioflavin T (ThT) and PPESO3-Nile Red (NR). Pattern recognition was achieved by linear discriminant analysis and hierarchical clustering analysis algorithms. As a result of distinguishing among monomers and three pure aggregate species, namely oligomers, protofibrils, and fibrils, the cross-reactive sensor array was also able to monitor aggregation kinetics in various aggregate forms and distinguish between on-and off-aggregate pathways. Our study provides a convenient approach for simultaneous detection of Aβ aggregates in mixtures, which may also be applied to the analysis of other disease-related proteins that are prone to aggregates.