Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy

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 mi...

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Bibliographic Details
Published in:Biomedical optics express 2020-09, Vol.11 (9), p.4989-5002
Main Authors: Ni, Ruiqing, Chen, Zhenyue, Gerez, Juan A., Shi, Gloria, Zhou, Quanyu, Riek, Roland, Nilsson, K. Peter R., Razansky, Daniel, Klohs, Jan
Format: Article
Language:English
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Summary: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.
ISSN:2156-7085
2156-7085
DOI:10.1364/BOE.395803