A dual-functional fluorescence probe for detection of Aβ aggregates and hydroxyl radicals

Synchronous detection of A beta aggregates and reactive oxygen species (ROS) would provide direct insight to reveal the complicated correlations between the two crucial Alzheimer's disease (AD) hallmarks. Herein, the first fluorescence probe (Quin-HCy) for dual-functional detection of A beta aggregates and the highly destructive ROS hydroxyl radicals (center dot OH) is developed. Quin-HCy is designed with a blood-brain barrier (BBB) permeable quinoline fluorophore and a center dot OH-responsive hydrocyanine moiety. Quin-HCy shows obvious fluorescence increases in response to A beta aggregates and center dot OH at 450 nm and 770 nm, respectively. The large spectral shift (similar to 320 nm) is advantageous for the independent detection of these two analytes in two distant channels. Quin-HCy has been used to image center dot OH in cells through the addition of Fenton reagents, stimulation with PMA and induction of ferroptosis. Most importantly, fluorescence imaging with Quin-HCy shows that significant center dot OH is generated in A beta aggregate-treated neuron cells, which provides direct evidence for the high dependence between A beta aggregates and center dot OH in the etiology of AD. Besides, Quin-HCy has favorable BBB permeability, and is able to image A beta plaques and center dot OH in AD mice brain slices.

Automated summary

A new dual-functional fluorescence probe Quin-HCy was developed to simultaneously detect A beta aggregates and ROS hydroxyl radicals. The significant correlation between A beta aggregates and ROS hydroxyl radicals in the etiology of AD was directly evidenced.