Dicyano-derivatives as mapping agents for peripheric Aβ plaques in Alzheimer’s disease mouse model

Abstract

Abnormal accumulation amyloid-β (Aβ) is recognized as one of the crucial factors for the progression and pathology of AD, which has accelerated the development of new chemical agents or technology for early mapping and monitoring Aβ plagues. While Aβ plaques is from diffuse to highly compacted (dense-core), most of reported dyes or probes could only stain the core of Aβ, due to the lack of monitoring technology, the research on periphery of Aβ was always ignored. Herein, we reported a new near-infrared (NIR) fluorescent probe named Dicyano-3, which had the capability to stain both core and periphery of Aβ plaques. Dicyano-3 was based on dicayno-scaffold and input N,N’-dimethyl group connecting with double bond. Meanwhile, cyclopropyl group applied in drug discovery was introduced to the structure which could lead to good photophysical properties. Dicyano-3 displayed good binding affinity for Aβ aggregates and better histological staining capability compared to Thioflavin T. Furthermore, Dicyano-3 showed good blood–brain barrier (BBB) permeability and low cytotoxicity. More importantly, in vivo imaging results indicate that the fluorescent intensity in the brain in 10-month APP/PS1 mice is higher than age-matched wild type mice. We believe that Dicyano-3 is benefit for the research of Aβ mechanism and AD drug discovery.

Keywords

• Alzheimer’s disease
• Amyloid-β aggregates
• NIRF probe
• Blood–brain barrier