A High-Affinity NIR Fluorescent Probe for Aβ Oligomers Enables Theranostics Through Disrupting Membrane Interaction...

Area of Science:

• Biochemistry
• Neuroscience
• Materials Science

Background:

• Amyloid-β (Aβ) oligomers are key biomarkers and therapeutic targets in Alzheimer's disease (AD) due to their neurotoxicity.
• Early detection and intervention are crucial for managing AD progression.

Purpose of the Study:

• To develop and characterize a novel D-π-A amphiphilic fluorescent probe for simultaneous detection and therapeutic modulation of Aβ oligomers.
• To evaluate the probe's efficacy in inhibiting Aβ aggregation and reducing Aβ-induced neurotoxicity.

Main Methods:

• Synthesis and characterization of the D-π-A amphiphilic fluorescent probe (API-QB).
• Assessment of API-QB's selectivity and sensitivity for Aβ oligomers in solution and simulated brain environments using fluorescence spectroscopy.
• Evaluation of API-QB's inhibitory effects on Aβ aggregation and Aβ oligomer-induced neurotoxicity, including cell membrane interaction and reactive oxygen species (ROS) production.

Main Results:

• The lead compound, API-QB, exhibits near-infrared (NIR) emission at 720 nm upon binding to Aβ oligomers.
• API-QB demonstrates high selectivity and sensitivity, with a dissociation constant (Kd) of 6.38 nM and a 47-fold fluorescence enhancement.
• API-QB effectively inhibits Aβ aggregation, reduces Aβ oligomer-cell membrane interactions, and suppresses ROS production, thereby mitigating Aβ oligomer toxicity.

Conclusions:

• The multifunctional probe API-QB shows significant potential for integrated diagnostic imaging and therapeutic intervention in Alzheimer's disease.
• API-QB's ability to detect and neutralize toxic Aβ oligomers offers a novel strategy for AD management.
• The probe's NIR emission and high binding affinity make it a promising candidate for advanced AD diagnostics and treatments.