Imaging hydrogen peroxide in Alzheimer's disease via cascade signal amplification

In brains of Alzheimer's disease (AD), reactive oxygen species (ROS) levels are significantly higher than that of healthy brains. Evidence suggests that, during AD onset and progression, a vicious cycle revolves around amyloid beta (Aβ) production, aggregation, plaque formation, microglia/immunological responses, inflammation, and ROS production. In this cycle, ROS species play a central role, and H₂O₂ is one of the most important ROS species. In this report, we have designed a fluorescent imaging probe CRANAD-88, which is capable of cascade amplifying near infrared fluorescence (NIRF) signals at three levels upon interacting with H₂O₂ in AD brains. We demonstrated that the amplification was feasible in vitro and in vivo. Remarkably, we showed that, for the first time, it was feasible to monitor the changes of H₂O₂ concentrations in AD brains before and after treatment with an H₂O₂ scavenger. Our method opens new revenues to investigate H₂O₂ in AD brains and can be very instructive for drug development.