Curcumin Complex Analogues as Near-Infrared Fluorescent Probes for Monitoring all Aβ Species in the Early Alzheimer's Disease Model

Aggregation of amyloid beta-peptide (A beta) is closely related to the pathology of Alzheimer's disease (AD). In this pathology, the beginning stage is characterized by excessive accumulation of A beta monomers due to imbalanced A beta in the process of clearance. The A beta peptide exists in many forms such as soluble and insoluble A beta species, both of which coexist during the progression of AD and contribute to AD pathology. Thus, probes capable of monitoring all A beta species are highly desirable. While there are several fluorescent probes for detecting insoluble A beta, it is still challenging to monitor all A beta forms by using probes. Here, we describe a near-infrared fluorescent chemical probe, termed AD-1, developed through complexation of curcumin analogues with a stabilizer, which has good photophysical properties and shows high binding to all A beta species in solution tests. Furthermore, AD-1 exhibited good blood-brain barrier penetrating ability and low cytotoxicity. More importantly, it was successfully applied to 4-month-young APP/PS1 mice imaging noninvasively.