A dicyanoisophorone-based probe with two-photon absorption and NIR emission was developed for the in vivo fluorescence imaging of amyloid-beta plaques, which exhibited high selectivity toward A beta aggregates over other intracellular proteins. The detection limit was calculated to be as low as 109 nM. In vivo imaging studies indicated that the probe could penetrate the blood brain barrier and label A beta plaques in the living transgenic mice, and its specific binding to cerebral A beta plaques was further confirmed by one and two-photon ex vivo fluorescence imaging. All these results featured its promising application prospects for amyloid-beta sensing in basic research and biomedical research. (C) 2017 Elsevier B.V. All rights reserved.