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.