Journal
ANALYTICAL CHEMISTRY
Volume 87, Issue 9, Pages 4781-4787Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.5b00017
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Funding
- National Natural Science Foundation. of China [81402891]
- Ph.D. Programs Foundation of Ministry of Education of China [20130181120114]
- Scientific Research Foundation for Youth Scholars from Sichuan University [2012SCU11091]
- China Postdoctoral Science Foundation [2014M560723]
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In vivo detection of cerebral beta-amyloid fibrils may facilitate the monitoring of beta-amyloidosis in the brain and effectiveness of antiamyloid therapies. Thioflavin T (ThT) is a widely used dye for the spectroscopic determination of beta-amyloid fibrils, but its ability to detect cerebral beta-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 beta-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 beta-amyloid fibrils. PAD-1 displayed a turn-on effect, showing significant enhancement in fluorescence when bound to the aggregated beta-amyloid fibrils. It also showed specific labeling of beta-amyloid deposits in APP/PS I transgenic mouse brains. Thus, PAD-1 proved to be a valuable alternative to ThT for cerebral beta-amyloid detection and may enable quantitative imaging in vivo.
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