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

[Image: see text] 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-β (Aβ) in Alzheimer’s disease (AD). Tools that can directly detect and monitor the presence and amount of Aβ-induced ROS are still lacking. We report herein the first Aβ-targeted ratiometric H(2)O(2)-responsive fluorescent probe for real-time detection and monitoring of the Aβ-induced H(2)O(2) level in cell and AD mouse models. The H(2)O(2)-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 ∼87 nm upon reacting with H(2)O(2), a high binding selectivity for Aβ, and a faster response toward H(2)O(2) in the presence of Aβ, concomitant with an enhanced fluorescence intensity, hence greatly boosting the sensitivity of in-situ H(2)O(2) detection. This biocompatible and nontoxic probe is capable of ratiometrically detecting and imaging endogenous H(2)O(2) induced by Aβ in a neuronal cell model. Remarkably, this Aβ-targeted H(2)O(2)-responsive probe is also able to detect, monitor, and differentiate different Aβ-induced H(2)O(2) levels in real time in different age groups of transgenic AD mice in which the cerebral H(2)O(2) 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.