摘要： High-fidelity mapping of amyloid-β (Aβ) plaques is critical for the early detection of Alzheimer’s disease. However, in vivo probing of Aβ plaques by commercially available Thioflavin derivatives (ThT or ThS) has proven to be extremely limited, as evident by the restriction of enrichment quenching effect, low signal-to-noise (S/N) ratio and poor blood-brain barrier (BBB) penetrability. Herein, we demonstrate a rational design strategy of near-infrared (NIR) aggregation-induced emission (AIE)-active probes for Aβ plaques, through introducing lipophilic π-conjugated thiophene-bridge for extending to NIR wavelength with enhancement of BBB penetrability, and tuning the substituted position of sulfonate group for guaranteeing specific hydrophilicity to keep fluorescence-off state before binding to Aβ deposition. Probe QM-FN-SO3 has well settled the AIE dilemma between lipophilic requirement for longer emission and aggregation behavior from water to protein fibrillogenesis, thus making a breakthrough in high-fidelity feedback on in vivo detection of Aβ plaques with remarkable binding affinity, and serving as an efficient alternative to the commercial probe ThT or ThS.