First Author | Kim D | Year | 2020 |
Journal | PLoS One | Volume | 15 |
Issue | 12 | Pages | e0243041 |
PubMed ID | 33362250 | Mgi Jnum | J:300168 |
Mgi Id | MGI:6491349 | Doi | 10.1371/journal.pone.0243041 |
Citation | Kim D, et al. (2020) Fluorescent indolizine derivative YI-13 detects amyloid-beta monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model. PLoS One 15(12):e0243041 |
abstractText | Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-beta (Abeta) peptides in the brain. Accumulated Abeta 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 Abeta-indicator YI-13, 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2-b]isoquinolin-9(6H)-one, which detects Abeta 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 Abeta as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Abeta plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Abeta 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 Abeta. |