An Iodinated BODIPY-Based Probe for the Selective Mapping and Disassembly of Amyloid-β Aggregates In Vivo

Area of Science:

• Neuroscience
• Chemistry
• Biomedical Engineering

Background:

• Alzheimer's disease (AD) is characterized by neurotoxic amyloid-β (Aβ) aggregates.
• Targeted photooxygenation is a promising strategy for degrading Aβ aggregates.

Purpose of the Study:

• To develop an iodinated BODIPY-based probe (BocIBDP) for selective mapping and photooxygenation of Aβ aggregates.
• To investigate BocIBDP's efficacy in Aβ plaque reduction and cognitive improvement in vivo.

Main Methods:

• Synthesis and characterization of the iodinated BODIPY probe (BocIBDP).
• Assessment of BocIBDP's binding affinity and selectivity for Aβ aggregates.
• Evaluation of BocIBDP-induced reactive oxygen species (ROS) generation upon Aβ binding.
• In vivo studies in APP/PS1 mice to evaluate plaque clearance and cognitive function.

Main Results:

• BocIBDP demonstrated selective mapping of Aβ aggregates with high affinity (Kd = 125.9 nM).
• Iodine incorporation enhanced BocIBDP's ROS generation via intersystem crossing.
• Aβ binding amplified BocIBDP's ROS-generating capacity, facilitating photodynamic oxidation.
• In vivo studies showed BocIBDP selectively stained Aβ plaques, reduced Aβ deposition, and alleviated cognitive deficits in APP/PS1 mice.

Conclusions:

• BocIBDP is a potent dual-function probe for Alzheimer's disease.
• It enables selective Aβ plaque imaging and therapeutic photooxygenation.
• BocIBDP holds potential for early AD diagnosis and treatment intervention.