Open AccessFluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model
Author(s) -
Da Won Kim,
Jeong Hwa Lee,
Hye Yun Kim,
Jisu Shin,
Kyeonghwan Kim,
Se-Jin Lee,
Jin-Woo Park,
Jin Ikyon Kim,
Young Soo Kim
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0243041
Subject(s) - indolizine , genetically modified mouse , fluorescence , monomer , amyloid (mycology) , chemistry , oligomer , senile plaques , microbiology and biotechnology , transgene , alzheimer's disease , biochemistry , biophysics , biology , pathology , medicine , stereochemistry , gene , disease , inorganic chemistry , physics , organic chemistry , quantum mechanics , polymer
Alzheimer disease (AD) is a neurodegenerative disorder characterized by the aberrant production and accumulation of amyloid-β (Aβ) peptides in the brain. Accumulated Aβ 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 Aβ-indicator YI-13 , 5-(4-fluorobenzoyl)-7,8-dihydropyrrolo[1,2- b ]isoquinolin-9(6 H )-one, which detects Aβ 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 Aβ as a target and YI-13 was selected as the final imaging candidate. YI-13 was found to stain and visualize insoluble Aβ plaques in the brain tissue, of a transgenic mouse model with five familial AD mutations (5XFAD), by a histochemical approach and to label soluble Aβ 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 Aβ.