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

Citation metadata

Date: Dec. 23, 2020
From: PLoS ONE(Vol. 15, Issue 12)
Publisher: Public Library of Science
Document Type: Report
Length: 8,970 words
Lexile Measure: 1460L

Document controls

Main content

Abstract :

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].

Source Citation

Source Citation   

Gale Document Number: GALE|A646422117