Fluorescent indolizine derivative YI-13 detects amyloid-β monomers, dimers, and plaques in the brain of 5XFAD Alzheimer transgenic mouse model

Da Won Kim, Jeong Hwa Lee, Hye Yun Kim, Jisu Shin, Kyeonghwan Kim, Sejin Lee, Jinwoo Park, Jin Ikyon Kim, Young Soo Kim

Research output: Contribution to journalArticlepeer-review

Abstract

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(6H)-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.

Original languageEnglish
Article numbere0243041
JournalPloS one
Volume15
Issue number12 December
DOIs
Publication statusPublished - 2020 Dec

Bibliographical note

Funding Information:
Korea Health Industry Development Institute (HI18C0836)(URL:https://www.khidi.or. kr) awarded to YK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. - National Research Foundation of Korea (Basic Science Research Program NRF2018R1A6A1A03023718, Original Technology Research Program for Brain Science NRF2018M3C7A1021858)(URL:http://www.nrf.re.kr) awarded to YK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. - National Research Foundation of Korea (NRF2020R1A2C2005961)(URL:http://www.nrf.re.kr) awarded to IK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. - POSCO TJ Park Foundation (POSCO Science Fellowship) (URL:https://www.postf.org) awarded to YK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. - The funder, BioActs, provided support in the form of salaries for author J. Park, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.

Publisher Copyright:
Copyright © 2020 Kim et al.

All Science Journal Classification (ASJC) codes

  • General

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