Highly Sensitive Near-Infrared Fluorophores for in Vivo Detection of Amyloid-β Plaques in Alzheimer's Disease

Alzheimer's disease (AD) is pathologically characterized by the accumulation of beta-amyloid (A beta) deposits in the parenchymal and cortical brain. In this work, we designed, synthesized, and evaluated a series of near-infrared (NIR) probes with electron donor-acceptor end groups interacting through a pi-conjugated system for the detection of A beta deposits in the brain. Among these probes, 3b and 3c had excellent fluorescent properties (emission maxima > 650 nm and high quantum yields) and displayed high sensitivity and high affinities to A beta aggregates (3b, K-d = 8.8 nM; 3c, K-d = 1.9 nM). Both 3b and 3c could readily penetrate the blood brain barrier with high initial brain uptake and fast to moderate washout from the brain. In vivo NIR imaging revealed that 3b and 3c could efficiently differentiate transgenic and wild-type mice. In summary, our research provides new hints for developing smarter and more activatable NIR probes targeting A beta.