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Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence
Ruiqing Ni1,2, Zhenyue Chen1,3, Juan A Gerez4
1University of Zurich & ETH Zurich, Institute for Biomedical Engineering, Department of Information Technology and Electrical Engineering, Wolfgang-Pauli-strasse 27 HIT E22.4, 8093, Zurich, Switzerland.
Abstract:
Current intravital microscopy techniques visualize tauopathy with high-resolution, but have a small field-of-view and depth-of-focus. Herein, we report a transcranial detection of tauopathy over the entire cortex of P301L tauopathy mice using large-field multifocal illumination (LMI) fluorescence microscopy technique and luminescent conjugated oligothiophenes. In vitro assays revealed that fluorescent ligand h-FTAA is optimal for in vivo tau imaging, which was confirmed by observing elevated probe retention in the cortex of P301L mice compared to non-transgenic littermates. Immunohistochemical staining further verified the specificity of h-FTAA to detect tauopathy in P301L mice. The new imaging platform can be leveraged in pre-clinical mechanistic studies of tau spreading and clearance as well as longitudinal monitoring of tau targeting therapeutics.
Insights
Researchers developed a new transcranial fluorescence microscopy technique to visualize tauopathy across the entire mouse cortex. This method offers a larger field-of-view for studying tau spreading and potential treatments.
Area of Science:
- Neuroscience
- Biomedical Imaging
- Biochemistry
Background:
- Current intravital microscopy for tauopathy has limitations in field-of-view and depth-of-focus.
- Tauopathy, a hallmark of neurodegenerative diseases like Alzheimer's, requires advanced imaging techniques for effective study.
Purpose of the Study:
- To develop and validate a novel transcranial fluorescence microscopy technique for large-scale tauopathy visualization.
- To identify an optimal fluorescent ligand for in vivo tau imaging.
Main Methods:
- Utilized large-field multifocal illumination (LMI) fluorescence microscopy.
- Employed luminescent conjugated oligothiophenes, specifically the h-FTAA ligand, for tau detection.
- Validated probe specificity and efficacy using P301L tauopathy mouse models and immunohistochemistry.
Main Results:
- Demonstrated transcranial detection of tauopathy across the entire cortex of P301L mice.
- Identified h-FTAA as an optimal fluorescent ligand for in vivo tau imaging, showing higher retention in tauopathy models.
- Confirmed the specificity of h-FTAA for tau detection in P301L mice.
Conclusions:
- The new LMI fluorescence microscopy platform enables whole-cortex visualization of tauopathy in vivo.
- This technique is valuable for pre-clinical research on tau spreading, clearance mechanisms, and therapeutic interventions.
- Facilitates longitudinal monitoring of tau-targeting treatments in neurodegenerative disease models.
