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Issue 20, 2020
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Differentiating Aβ40 and Aβ42 in amyloid plaques with a small molecule fluorescence probe

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Abstract

Differentiating amyloid beta (Aβ) subspecies Aβ40 and Aβ42 has long been considered an impossible mission with small-molecule probes. In this report, based on recently published structures of Aβ fibrils, we designed iminocoumarin–thiazole (ICT) fluorescence probes to differentiate Aβ40 and Aβ42, among which Aβ42 has much higher neurotoxicity. We demonstrated that ICTAD-1 robustly responds to Aβ fibrils, evidenced by turn-on fluorescence intensity and red-shifting of emission peaks. Remarkably, ICTAD-1 showed different spectra towards Aβ40 and Aβ42 fibrils. In vitro results demonstrated that ICTAD-1 could be used to differentiate Aβ40/42 in solutions. Moreover, our data revealed that ICTAD-1 could be used to separate Aβ40/42 components in plaques of AD mouse brain slides. In addition, two-photon imaging suggested that ICTAD-1 was able to cross the BBB and label plaques in vivo. Interestingly, we observed that ICTAD-1 was specific toward plaques, but not cerebral amyloid angiopathy (CAA) on brain blood vessels. Given Aβ40 and Aβ42 species have significant differences of neurotoxicity, we believe that ICTAD-1 can be used as an important tool for basic studies and has the potential to provide a better diagnosis in the future.

Graphical abstract: Differentiating Aβ40 and Aβ42 in amyloid plaques with a small molecule fluorescence probe

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Supplementary files

Article information


Submitted
13 Apr 2020
Accepted
29 Apr 2020
First published
11 May 2020

This article is Open Access
All publication charges for this article have been paid for by the Royal Society of Chemistry

Chem. Sci., 2020,11, 5238-5245
Article type
Edge Article

Differentiating Aβ40 and Aβ42 in amyloid plaques with a small molecule fluorescence probe

J. Yang, B. Zhu, W. Yin, Z. Han, C. Zheng, P. Wang and C. Ran, Chem. Sci., 2020, 11, 5238
DOI: 10.1039/D0SC02060E

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