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

Ruiqing Ni; Zhenyue Chen; Juan A Gerez; Gloria Shi; Quanyu Zhou; Roland Riek; K Peter R Nilsson; Daniel Razansky; Jan Klohs

doi:10.1364/BOE.395803

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

Biomed Opt Express. 2020 Aug 11;11(9):4989-5002. doi: 10.1364/BOE.395803. eCollection 2020 Sep 1.

Authors

Ruiqing Ni^{1

2}, Zhenyue Chen^{1

3}, Juan A Gerez⁴, Gloria Shi¹, Quanyu Zhou^{1

3}, Roland Riek⁴, K Peter R Nilsson⁵, Daniel Razansky^{1

2

3}, Jan Klohs^{1

2}

Affiliations

¹ University 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.
² University of Zurich, Zurich Neuroscience Center, Zurich, Switzerland.
³ University of Zurich, Faculty of Medicine and Institute of Pharmacology and Toxicology, Zurich, Switzerland.
⁴ ETH Zurich, Laboratory of Physical Chemistry, Department of Chemistry and Applied Biosciences, Zurich, Switzerland.
⁵ Linköping University, Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping, Sweden.

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.