Dynamic Visualization of Amyloid-β Plaques with a Novel NIR-II Fluorescence Reporter

Alzheimer's disease (AD), a progressive neurodegenerative disorder, represents a major global health challenge for aging populations. As amyloid-β (Aβ) plaques are pathological hallmarks of AD, their efficient detection is critical for disease staging and early diagnosis. However, existing fluorescent probes are hindered by a weak signal response to Aβ plaques, short-emission wavelengths, and insufficient blood-brain barrier (BBB) penetration, which preclude effective in vivo imaging. To address these limitations, we developed a novel series of second near-infrared window (NIR-II) probes, termed CoR-Aβs, engineered for high-affinity binding to Aβ fibrils. Demonstrating exceptional BBB permeability, our lead compound, CoR-Aβ-4, enables real-time dynamic tracking of plaque deposition in vivo. This work establishes NIR-II fluorescent probes as a transformative platform for advancing diagnostic strategies in neurodegenerative disease intervention.