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Dual-Emission GFP Chromophore-Based Derivative for Imaging and Discriminating Aβ Oligomers and Aggregates.

Huaxiang LengYuxuan WangJuan WangHan SunAnyang SunMarco PistolozziLei ZhangJin-Wu Yan
Published in: Analytical chemistry (2022)
β-Amyloid deposition is one of the main pathological features of Alzheimer's disease (AD). The development of fluorescent probes targeting specific β-amyloid species has recently become an attractive strategy to achieve the early diagnosis of AD. In this work, a dual-channel fluorescent protein chromophore derivative C17 was rationally designed and synthesized for the detection and discrimination of Aβ 42 aggregates and oligomers. C17 exhibits a specific turn-on emission peak for Aβ 42 oligomers at ∼470 nm (peak A) and a peak at ∼600 nm (peak B) for both Aβ 42 oligomers and Aβ 42 aggregates. Taking advantage of the dual emission of the probe, the dynamic aggregation process of the Aβ 42 peptide was monitored in solution. Moreover, double staining of brain sections from transgenic AD mice revealed that peak A of C17 preferentially detected Aβ 42 oligomers, whereas peak B was more sensitive to Aβ 42 aggregates. The fact that probe C17 can be used for dissecting these two Aβ 42 species makes C17 a comprehensive tool for β-amyloid aggregation studies in AD research.
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