Fluorescent imaging of β-amyloid (Aβ) is one of the most promising methods for Alzheimer’s disease diagnosis. Several fluorescent probes have been reported to detect Aβ both in vitroand in vivo.However, highly sensitive and highly selective probes with low background signals are still greatly needed. Herein, we rationally designed and synthesized a PIET quenched near-infrared probe QAD-1to detect Aβ. This probe contains BODIPY as fluorophore and tetrahydroquinoxaline as the quenching group. QAD-1exhibited significant fluorescent switch-on after binding to soluble and insoluble Aβ species, and the probe had the benefit of low background signal to stain Aβ plaques without the need of wash-out procedures in vitro, which was specially found by the fluorescence off–on probe. QAD-1could identify the overproduced Aβ in transgenic (APPSWE/PSEN 1dE9) AD mice as early as 6 months old in vivo, which indicated that QAD-1may be a potential probe for monitoring Aβ species at an early stage of AD.