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Updated: Sep 4, 2025
Detecting Amyloid-β Accumulation via Immunofluorescent Staining in a Mouse Model of Alzheimer's Disease
Published on: April 19, 2021
Multiscale optical and optoacoustic imaging of amyloid-β deposits in mice
Ruiqing Ni1,2,3, Zhenyue Chen1,4, Xosé Luís Deán-Ben1,4
1Institute for Biomedical Engineering, University of Zurich and ETH Zurich, Zurich, Switzerland.
Abstract:
Deposits of amyloid-β (Aβ) in the brains of rodents can be analysed by invasive intravital microscopy on a submillimetre scale, or via whole-brain images from modalities lacking the resolution or molecular specificity to accurately characterize Aβ pathologies. Here we show that large-field multifocal illumination fluorescence microscopy and panoramic volumetric multispectral optoacoustic tomography can be combined to longitudinally assess Aβ deposits in transgenic mouse models of Alzheimer's disease. We used fluorescent Aβ-targeted probes (the luminescent conjugated oligothiophene HS-169 and the oxazine-derivative AOI987) to transcranially detect Aβ deposits in the cortex of APP/PS1 and arcAβ mice with single-plaque resolution (8 μm) and across the whole brain (including the hippocampus and the thalamus, which are inaccessible by conventional intravital microscopy) at sub-150 μm resolutions. Two-photon microscopy, light-sheet microscopy and immunohistochemistry of brain-tissue sections confirmed the specificity and regional distributions of the deposits. High-resolution multiscale optical and optoacoustic imaging of Aβ deposits across the entire brain in rodents thus facilitates the in vivo study of Aβ accumulation by brain region and by animal age and strain.
Insights
This study introduces a novel multiscale imaging technique to track amyloid-β (Aβ) deposits in mouse brains. This method allows for high-resolution, whole-brain visualization of Alzheimer's disease pathologies in vivo.
Area of Science:
- Neuroscience
- Medical Imaging
- Biomedical Engineering
Background:
- Amyloid-β (Aβ) deposits are key hallmarks of Alzheimer's disease (AD).
- Current methods for analyzing Aβ in rodent models have limitations in scale, resolution, or molecular specificity.
- Intravital microscopy offers high resolution but is limited to submillimeter scales, while whole-brain imaging lacks detailed characterization.
Purpose of the Study:
- To develop and validate a non-invasive, multiscale imaging approach for longitudinal assessment of Aβ deposits in the brain.
- To enable high-resolution, whole-brain characterization of Aβ pathologies in transgenic mouse models of AD.
- To overcome the limitations of existing imaging techniques for studying Aβ accumulation dynamics.
Main Methods:
- Combined large-field multifocal illumination fluorescence microscopy with panoramic volumetric multispectral optoacoustic tomography.
- Utilized fluorescent Aβ-targeted probes (HS-169 and AOI987) for transcranial detection.
- Validated findings using two-photon microscopy, light-sheet microscopy, and immunohistochemistry.
Main Results:
- Achieved single-plaque resolution (8 μm) in the cortex and sub-150 μm resolution across the whole brain, including deep structures like the hippocampus and thalamus.
- Successfully detected and longitudinally assessed Aβ deposits in APP/PS1 and arcAβ mouse models.
- Confirmed the specificity and regional distribution of Aβ deposits through correlative microscopy and histology.
Conclusions:
- The developed multiscale optical and optoacoustic imaging technique provides unprecedented in vivo capabilities for studying Aβ deposition.
- This method facilitates detailed, region-specific, and longitudinal analysis of Aβ accumulation across different ages and genetic backgrounds in rodent models.
- Enables advanced research into Alzheimer's disease pathogenesis and therapeutic interventions.
