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.

PubMed

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.