期刊
PLOS ONE
卷 15, 期 12, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0243041
关键词
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资金
- Korea Health Industry Development Institute [HI18C0836]
- National Research Foundation of Korea (Basic Science Research Program) [NRF-2018R1A6A1A03023718, NRF-2018M3C7A1021858]
- National Research Foundation of Korea [NRF-2020R1A2C2005961]
- POSCO TJ Park Foundation (POSCO Science Fellowship)
Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-beta (A beta) peptides in the brain. Accumulated A beta in soluble oligomer and insoluble plaque forms are considered to be a pathological culprit and biomarker of the disorder. Here, we report a fluorescent universal A beta-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects A beta monomers, dimers, and plaques. We synthesized a library of 26 fluorescence chemicals with the indolizine core and screen them through a series of in vitro tests utilizing A beta as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble A beta plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble A beta oligomers within brain lysates of the mouse model under a fluorescence plate reader. Among oligomers aggregated from monomers and synthetic dimers from chemically conjugated monomers, YI-13 preferred the dimeric A beta.
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