Real-Time Detection and Visualization of Amyloid-β Aggregates Induced by Hydrogen Peroxide in Cell and Mouse Models of Alzheimer's Disease

Oxidative stress, caused by an imbalance between the production and the accumulation of reactive oxygen species (ROS), is a prominent cause of the neurotoxicity induced by aggregated amyloid-beta (A beta) in Alzheimer's disease (AD). Tools that can directly detect and monitor the presence and amount of A beta-induced ROS are still lacking. We report herein the first A beta-targeted ratiometric H2O2-responsive fluorescent probe for real-time detection and monitoring of the A beta-induced H2O2 level in cell and AD mouse models. The H2O2-responsive probe is constructed based on a methylamino-substituted quinolinium-based cyanine as the fluorescence moiety and a phenylboronate ester as the sensing reaction site. This sensing probe exhibits a large emission wavelength shift of similar to 87 nm upon reacting with H2O2, a high binding selectivity for A beta, and a faster response toward H2O2 in the presence of A beta, concomitant with an enhanced fluorescence intensity, hence greatly boosting the sensitivity of in-situ H2O2 detection. This biocompatible and nontoxic probe is capable of ratiometrically detecting and imaging endogenous H2O2 induced by A beta in a neuronal cell model. Remarkably, this A beta-targeted H2O2-responsive probe is also able to detect, monitor, and differentiate different A beta-induced H2O2 levels in real time in different age groups of transgenic AD mice in which the cerebral H2O2 level increases age dependently concomitant with the plaque contents. Therefore, this smart probe can act as a powerful tool to diagnose high-risk subjects and diseased brains of AD and to further study the role of ROS in AD pathology.

Automated summary

This study reports the development of the first A beta-targeted ratiometric H2O2-responsive fluorescent probe for real-time detection and monitoring of A beta-induced H2O2 levels. This probe can be used as a powerful tool for diagnosing high-risk subjects and diseased brains of AD, as well as studying the role of ROS in AD pathology.