In Vivo Detection of Cerebral Amyloid Fibrils with Smart Dicynomethylene-4H-Pyran-Based Fluorescence Probe

In vivo detection of cerebral β-amyloid fibrils may facilitate the monitoring of β-amyloidosis in the brain and effectiveness of antiamyloid therapies. Thioflavin T (ThT) is a widely used dye for the spectroscopic determination of β-amyloid fibrils, but its ability to detect cerebral β-amyloid fibrils in vivo is limited due to the charged molecule. To this end, a smart dicynomethylene-4H-pyran (DCM) fluorophore, namely, (E)-2-(2-(4-(dimethylamino)styryl)-6-methyl-4H-pyran-4-ylidene) malononitrile (PAD-1), was evaluated for in vivo fluorescence imaging of cerebral β-amyloid fibrils. PAD-1 rapidly entered the brain with high initial brain uptake after intravenous injection, which is highly desirable for in vivo detection of β-amyloid fibrils. PAD-1 displayed a turn-on effect, showing significant enhancement in fluorescence when bound to the aggregated β-amyloid fibrils. It also showed specific labeling of β-amyloid deposits in APP/PS1 transgenic mouse brains. Thus, PAD-1 proved to be a valuable alternative to ThT for cerebral β-amyloid detection and may enable quantitative imaging in vivo.