Real-Time Monitoring of Self-Aggregation of β-Amyloid by a Fluorescent Probe based on Ruthenium Complex

Self-accumulation of amyloid-β protein (Aβ) into insoluble fibrils is the major hallmark of Alzheimer’s disease. Real-time monitoring of fibril growth is essential for clarifying the mechanism underlying aggregation and discovering therapeutic targets. A variety of approaches including NMR, Electron microscopy (EM), atomic force microscopy (AFM) and total internal reflection fluorescence microscopy (TIRFM) have been explored to monitor the fibril growth or reveal morphology of Aβ aggregates. However, none of the methods allow real-time observation under physiological conditions while without any perturbations. Here, we present a fluorescent probe [Ru(phen)2(fipc)]2+ (Ru-fipc) (phen = 1,10-phenanthroline, fipc = 5-fluoro-N- (1,10-phenanthrolin-5-yl)-1H-indole-2-carboxamide), that can bind to all the Aβ forms, i.e., monomers, oligomers and fibrils, while not perturb aggregation. Using this probe in combination with laser confocal microscopy, the entire aggregation process could be clearly and exactly imaged...