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bioRxiv · 10.1101/2020.05.18.101188

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

Ni, R.·Chen, Z.·GEREZ, J. A.·Shi, G.·Zhou, Q.·Riek, R.·Nilsson, P. R.·Razansky, D.·Klohs, J.
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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.

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Ni, R., Chen, Z., GEREZ, J. A., Shi, G., Zhou, Q., Riek, R., Nilsson, P. R., Razansky, D., Klohs, J.. 2020-05-19. Detection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy. https://doi.org/10.1101/2020.05.18.101188

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