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

Area of Science:

• Neuroscience
• Biomedical Imaging
• Molecular Probes

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder posing a significant global health challenge.
• Amyloid-beta (Aβ) plaques are key pathological hallmarks of AD, making their detection crucial for diagnosis and staging.
• Current fluorescent probes for Aβ detection suffer from weak signals, short emission wavelengths, and poor blood-brain barrier (BBB) penetration, limiting in vivo imaging.

Purpose of the Study:

• To develop novel second near-infrared window (NIR-II) fluorescent probes for high-affinity binding to Aβ fibrils.
• To overcome the limitations of existing probes, including weak signals and insufficient BBB penetration.
• To enable real-time dynamic tracking of Aβ plaque deposition in vivo for improved AD diagnosis.

Main Methods:

• Synthesis and engineering of a novel series of NIR-II fluorescent probes, termed CoR-Aβs.
• Evaluation of probe affinity for Aβ fibrils.
• Assessment of BBB permeability and in vivo imaging capabilities of the developed probes.

Main Results:

• The developed CoR-Aβ probes exhibit high affinity for Aβ fibrils.
• The lead compound, CoR-Aβ-4, demonstrated exceptional BBB permeability.
• CoR-Aβ-4 enabled real-time dynamic tracking of Aβ plaque deposition in vivo.

Conclusions:

• Novel NIR-II fluorescent probes (CoR-Aβs) offer a promising solution for Aβ plaque detection in Alzheimer's disease.
• These probes overcome key limitations of existing imaging agents, enhancing diagnostic potential.
• NIR-II probes represent a transformative platform for advancing neurodegenerative disease diagnostic strategies.