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.
Highlights
The abnormal deposition of pathological tau fibrils is a characteristic feature of tauopathy related neurodegenerative diseases including Alzheimer’s disease, frontotemporal lobar dementia (FTLD), chronic traumatic encephalopathy, corticobasal degeneration, progressive supranuclear palsy and parkinsonism linked to chromosome 17 [1]
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
The luminescent conjugated oligothiophene (LCO) show different spectral characteristics when bound to tau fibrils, the detected emission peaks are for h-FTAA: 549 nm; q-FTAA: 530 nm; HS-84: 504 nm; and HS-169: 654 nm, respectively
Summary
The abnormal deposition of pathological tau fibrils is a characteristic feature of tauopathy related neurodegenerative diseases including Alzheimer’s disease, frontotemporal lobar dementia (FTLD), chronic traumatic encephalopathy, corticobasal degeneration, progressive supranuclear palsy and parkinsonism linked to chromosome 17 [1]. Tau abnormal accumulation in patients with Alzheimer’s disease was found to be closely related to axonal damage, neurodegeneration and cognitive impairment [3,4,5]. This designates tauopathy an important target for early diagnostic and therapeutic intervention for Alzheimer’s disease, FTLD, and other tauopathy disorders [6]. In vivo imaging of tauopathy was enabled by PET in
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