GFP-based red-emissive fluorescent probes for dual imaging of β-amyloid plaques and mitochondrial viscosity

Alzheimer's disease (AD), with incurable neurodegenerative damage, has attracted growing interest in exploration of better AD biomarkers in its early diagnosis. Among various biomarkers, amyloid-β (Aβ) aggregates and mitochondrial viscosity are closely related to AD and their dual imaging might provide a potential and feasible strategy. In this work, five GFP-based red-emissive fluorescent probes were rationally designed and synthesized for selective detection of β-amyloid plaques and viscosity, among which C25e exhibited superior properties and could successfully image β-amyloid plaques and mitochondrial viscosity with different fluorescence wavelength signals "turn-on" at around 624 and 640 nm, respectively. Moreover, the staining of brain sections from a transgenic AD mouse showed that probe C25e showed higher selectivity and signal-to-noise ratio towards Aβ plaques than commercially-available Thio-S. In addition, the probe C25e was, for the first time, employed for monitoring amyloid-β induced mitochondrial viscosity changes. Therefore, this GFP-based red-emissive fluorescent probe C25e could serve as a dual-functional tool for imaging β-amyloid plaques and mitochondrial viscosity, which might provide a unique strategy for the early diagnosis of Alzheimer's disease.