In this article, we first designed and synthesized curcumin-based near-infrared (NIR) fluorescence imaging probes for detecting both soluble and insoluble amyloid beta (A beta) species and then an inhibitor that could attenuate cross-linking of A beta induced by copper. According to our previous results and the possible structural stereohindrance compatibility of the A beta peptide and the hydrophobic/hydrophilic property of the A beta 13-20 (HHQKLVFF) fragment, NIR imaging probe CRANAD-58 was designed and synthesized. As expected CRANAD-58 showed significant fluorescence property changes upon mixing with both soluble and insoluble A beta species in vitro. In vivo NIR imaging revealed that CRANAD-58 was capable of differentiating transgenic and wild-type mice as young as 4 months old, the age that lacks apparently visible A beta plaques and A beta is likely in its soluble forms. According to our limited studies on the interaction mechanism between CRANAD-58 and A beta, we also designed CRANAD-17 to attenuate the cross-linking of A beta 42 induced by copper. It is well-known that the coordination of copper with imidazoles on Histidine-13 and 14 (H13, H14) of A beta peptides could initialize covalent cross-linking of A beta. In CRANAD-17, a curcumin scaffold was used as an anchoring moiety to usher the designed compound to the vicinity of H13 and H14 of A beta, and imidazole rings were incorporated to compete with H13/H14 for copper binding. The results of SDS-PAGE gel and Western blot indicated that CRANAD-17 was capable of inhibiting A beta 42 cross-linking induced by copper. This raises a potential for CRANAD-17 to be considered for AD therapy.