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

Abstract

Aggregation of amyloid β-peptide (Aβ) is closely related to the pathology of Alzheimer's disease (AD). In this pathology, the beginning stage is characterized by excessive accumulation of Aβ monomers due to imbalanced Aβ in the process of clearance. The Aβ peptide exists in many forms such as soluble and insoluble Aβ species, both of which coexist during the progression of AD and contribute to AD pathology. Thus, probes capable of monitoring all Aβ species are highly desirable. While there are several fluorescent probes for detecting insoluble Aβ, it is still challenging to monitor all Aβ 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 Aβ 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.