Open AccessDetection of cerebral tauopathy in P301L mice using high-resolution large-field multifocal illumination fluorescence microscopy
Author(s) -
Ruiqing Ni,
Zhenyue Chen,
Juan Gerez,
Gloria Shi,
Quanyu Zhou,
Roland Riek,
K. Peter R. Nilsson,
Daniel Razansky,
Jan Klohs
Publication year - 2020
Publication title -
biomedical optics express
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.362
H-Index - 86
ISSN - 2156-7085
DOI - 10.1364/boe.395803
Subject(s) - tauopathy , fluorescence microscope , microscopy , confocal microscopy , fluorescence lifetime imaging microscopy , pathology , biology , neuroscience , fluorescence , microbiology and biotechnology , optics , medicine , neurodegeneration , physics , disease
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.