Detection of Aβ oligomers in early Alzheimer’s disease diagnose by in vivo NIR-II fluorescence imaging

Diagnosing Alzheimer’s disease (AD) in its initial stage is critical for early intervention and treatment. Thus, discovering a probe capable of targeting Aβ oligomers, which are the biomarkers of early-stage AD, is highly desirable. Herein, we report a functional probe that responds to Aβ oligomers via second near-infrared window (NIR-II) fluorescence imaging. The molecular probe comprises N, N-diethylaniline as the recognition group, which also serves as a strong donor group, and a boron difluoride bridged azafluvene as a strong electron-withdrawing group. Molecular docking results indicated that the binding mode involves hydrogen bonds and π-π stacking with Phe residues in Aβ oligomers. Examination of the selectivity revealed that the probe was more responsive to Aβ oligomers (Kd = 6.16 nM) than Aβ fibrils and not responsive to other biomolecular small molecules. The low molecular weight of the probe facilitated rapid penetration of the blood-brain barrier. In vitro and in vivo studies indicated that the probe preferentially targets Aβ oligomers and reaches the hippocampus region. This report presents the first “D-A-D” type NIR-II fluorescence probe to target Aβ oligomers for in vivo AD early diagnosis.