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Summary
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New 3D histology methods enable whole-brain imaging of amyloid plaques and microglia in Alzheimer's disease models. This technology aids in developing central nervous system therapeutics by mapping neuroinflammation and plaque deposition.

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Area of Science:

  • Neuroscience
  • Histology
  • Drug Discovery

Background:

  • Traditional 2D histology limits deep tissue imaging to specific regions.
  • Advances in optical clearing and light sheet imaging enable 3D brain-wide cellular resolution.
  • 3D histology is crucial for CNS therapeutic development, assessing target engagement and efficacy.

Purpose of the Study:

  • To develop and disseminate advanced 3D tissue clearing and AI-powered quantification methodologies.
  • To enable brain-wide, cellular resolution analysis of amyloid plaques and microglia.
  • To facilitate unbiased mapping of CNS therapeutic efficacy in neuroinflammation and amyloid deposition.

Main Methods:

  • Utilized iDISCO-based tissue clearing kits and light sheet microscopy for intact mouse brain imaging.
  • Employed Translucence Teravoxel Toolkit (3TK) software for cell identification and 3D atlas registration.
  • Developed AI-powered workflows for segmenting microglia (Iba1) and quantifying amyloid plaques.

    • Main Results:

    • Achieved brain-wide segmentation of microglia, providing regional activation metrics.
    • Successfully labeled and quantified amyloid plaques in 5xFAD mouse models.
    • Identified and quantified plaque-associated microglia (PAMs), correlating their levels with plaque density.

    Conclusions:

    • Disseminated 3D histology technology via BRAIN Initiative-funded kits and cloud-based analysis.
    • Enables neuroscientists to utilize next-generation 3D immunohistochemistry for comprehensive CNS analysis.
    • Facilitates unbiased, anatomically precise mapping of therapeutic efficacy for amyloid and neuroinflammation.