Design, Synthesis, and Performance Characterization of BODIPY-Based NIR Probes for Aβ₄₂ Aggregate Detection

Area of Science:

• Neuroscience
• Chemistry

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by β-amyloid (Aβ) plaques.
• Early and accurate detection of cerebral Aβ aggregates is crucial for timely AD intervention but remains challenging.
• Existing near-infrared imaging tools lack the required sensitivity and signal-to-noise ratio for early Aβ pathological detection.

Purpose of the Study:

• To design and synthesize novel BODIPY-quinoline-based fluorescent probes for targeting Aβ42 aggregates.
• To evaluate the performance of these probes for early pathological imaging diagnosis of AD.

Main Methods:

• Synthesis of two BODIPY-quinoline-based fluorescent probes, BQ-1 and BQ-2.
• Assessment of probe affinity, sensitivity, and signal-to-noise ratio for Aβ42 aggregates.
• Evaluation of optical properties, including near-infrared fluorescence emission and Stokes shift.
• Cell imaging experiments using PC12 cells to assess selectivity and cytotoxicity.

Main Results:

• BQ-1 demonstrated high affinity (K_D = 48.81 nM) and sensitivity (LOD = 52 nM) for Aβ42 aggregates.
• BQ-1 exhibited a high signal-to-noise ratio (189.5-fold) and favorable near-infrared fluorescence emission (λex/λem = 612/669 nm).
• Cell imaging confirmed BQ-1's ability to selectively label Aβ42 aggregates with low cytotoxicity.

Conclusions:

• BQ-1 is a high-performance near-infrared fluorescent probe suitable for targeting Aβ42 aggregates.
• BQ-1 shows significant potential as a tool for early pathological imaging diagnosis of Alzheimer's disease.