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Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
Multiplex imaging of amyloid-β plaques dynamics in living brains with quinoline-malononitrile-based probes
Jianfeng Dai1,2, Weijun Wei3, Chenxu Yan4
1Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Institute of Fine Chemicals, Frontiers Science Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai, China.
Abstract:
The dynamic behaviour of amyloid-β (Aβ) plaques in Alzheimer's disease remains poorly understood, and accumulation and distribution of Aβ plaques must be inferred from in vitro pathological changes in brain tissue. In situ detection of Aβ plaques in live imaging is challenging because of the lack of adequate probes. Here we report the design of unimolecular quinoline-malononitrile-based Aβ probes, termed QMFluor integrative framework, that binds in vivo to Aβ plaques, making them detectable via near-infrared fluorescence imaging, magnetic resonance imaging, positron emission tomography and computed tomography. QMFluor probes are permeable to the blood-brain barrier, and, upon systematic injection, enable real-time magnetic resonance imaging and positron emission tomography-computed tomography imaging of the Aβ biodistribution in the hippocampus and cerebral cortex, and accurately differentiate the brains of living Alzheimer's disease mouse models from wild-type controls. We further demonstrate the ability of QMFluor probes to reach the brain after intravenous injection in a large animal model. This strategy expands the toolbox of probes for in vivo visualization of amyloids in Alzheimer's disease pathological analysis, drug screening and clinical applications.
Insights
Researchers developed novel QMFluor probes for real-time in vivo imaging of amyloid-beta (Aβ) plaques in Alzheimer's disease. These probes enable advanced diagnostics and drug screening by visualizing Aβ distribution across the brain.
Area of Science:
- Biomedical Imaging
- Neuroscience
- Molecular Probes
Background:
- Alzheimer's disease (AD) pathogenesis involves amyloid-beta (Aβ) plaque accumulation, but in vivo visualization is limited.
- Current methods rely on indirect inference from in vitro studies due to a lack of effective in situ probes.
Purpose of the Study:
- To design and validate novel probes for direct, real-time in vivo detection of Aβ plaques.
- To assess the probes' capability for multimodal imaging and brain penetration.
Main Methods:
- Development of unimolecular quinoline-malononitrile-based probes (QMFluor).
- Evaluation of blood-brain barrier permeability and in vivo binding to Aβ plaques.
- Utilizing near-infrared fluorescence, MRI, PET, and CT imaging modalities.
Main Results:
- QMFluor probes successfully bind to Aβ plaques in vivo, enabling detection via multiple imaging techniques.
- Probes demonstrate blood-brain barrier permeability, allowing real-time imaging of Aβ biodistribution in mouse models.
- Distinguished between Alzheimer's disease mouse models and wild-type controls, and showed brain penetration in a large animal model.
Conclusions:
- The QMFluor framework offers a versatile tool for in vivo amyloid imaging in Alzheimer's disease research.
- This strategy enhances pathological analysis, drug screening, and potential clinical applications for AD.
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