Aberrant accumulation of Amyloid-β (Aβ) peptide is closely related to Alzheimer's disease. Thus, it is important to develop featured probes for the specific detection of Aβ species. Herein, we designed and synthesized a novel near-infrared fluorescent probe SDPY based on the D-π-A architecture for the detection of Aβ aggregates. The probe SDPY displayed higher affinity for Aβ40 aggregates over Aβ42 aggregates in solution (Kd = 164 nM vs. 2.1 μM). In addition, SDPY showed excellent anti-interference against a wide range of other substances. Furthermore, SDPY was capable of labeling Aβ40 aggregates better than Aβ42 aggregates in the brain sections of AD transgenic mouse models.