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

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 Aβ₄₂ aggregates and oligomers. C17 exhibits a specific turn-on emission peak for Aβ₄₂ oligomers at ∼470 nm (peak A) and a peak at ∼600 nm (peak B) for both Aβ₄₂ oligomers and Aβ₄₂ aggregates. Taking advantage of the dual emission of the probe, the dynamic aggregation process of the Aβ₄₂ peptide was monitored in solution. Moreover, double staining of brain sections from transgenic AD mice revealed that peak A of C17 preferentially detected Aβ₄₂ oligomers, whereas peak B was more sensitive to Aβ₄₂ aggregates. The fact that probe C17 can be used for dissecting these two Aβ₄₂ species makes C17 a comprehensive tool for β-amyloid aggregation studies in AD research.