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[Display omitted] • New fluorescent probes (8a–d) were designed and synthesized based on a curcumin scaffold. • Probe 8b displayed an emission wavelength in the NIR region and a good binding affinity for the Aβ aggregates. • Probe 8b achieved clear visualization of Aβ plaques in 5XFAD transgenic mice. • The signal intensity of 8b in the brain of the 5XFAD mouse was much higher than that of the control group. • The biological uptake of 8b into the internal organs and brain was confirmed via ex vivo experiments. The abnormal self-assembly of amyloid-beta (Aβ) peptides into oligomers, as well as insoluble fibrils, has been identified as a key factor for monitoring the progression of Alzheimer's disease (AD). The noninvasive imaging of Aβ aggregates utilizing chemical probes can be a powerful and practical technique for accurately diagnosing and monitoring the progress of AD, as well as evaluating the effectiveness of therapeutic drug candidates in treating or managing it. Particularly, the near-infrared (NIR) fluorescence imaging of Aβ plaques is a potentially promising approach toward the efficient detection of the biomarker. In this study, we describe a new NIR fluorophore, which was based on curcumin derivatives. The fluorophore is equipped with desirable optical properties for in vivo brain imaging. The emission wavelength of the probe, 8b , is 667 nm, and its fluorescent intensity is significantly increased through binding with the Aβ aggregates. The probe allows the clear visualization of the Aβ plaques 10 min post administration, and the intensity of the fluorescent signal in the brain of a 5XFAD transgenic mouse model is more than three times higher than that of the normal control group. These results demonstrate that the designed probe can be an effective tool for visualizing Aβ plaques, as well as investigating the pathological progress of AD. [ABSTRACT FROM AUTHOR]