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Transcranial detection of tauopathy in vivo in P301L mice with high‐resolution large‐field multifocal illumination fluorescence microscopy


Ni, Ruiqing; Chen, Zhenyue; Gerez, Juan A; Shi, Gloria; Zhou, Quanyu; Riek, Roland; Nilsson, K Peter R; Razansky, Daniel; Klohs, Jan (2020). Transcranial detection of tauopathy in vivo in P301L mice with high‐resolution large‐field multifocal illumination fluorescence microscopy. Alzheimer's & Dementia, 16(S5):e047238.

Abstract

Background: Tau abnormal aggregates have been visualized in‐vivo using intravital microscopy techniques with high resolution, but are limited to a small field‐of‐view and depth. Here, we report a new method for the transcranial detection of tau deposits accross the brain with 6 μm resolution.
Method: In vitro Thioflavin T fluorescence assay was performed to screen fluorescence imaging probes that bind to tau fibrils. P301L (Thy1.2) mouse models of frontal temporal lobe dementia with four repeat tau and non‐transgenic littermates were imaged in vivo using a novel large‐field multifocal illumination (LMI) fluorescence microscopy technique using luminescent conjugated oligothiophenes h‐FTAA. Immunohistochemical staining were performed on P301L mouse brain tissue sections using anti‐phosphorylated tau antibodies AT8 and AT100.
Result: In vitro Thioflavin T fluorescence assay and LMI imaging shows that h‐FTAA bind to recombinant full‐length tau fibrils. In vivo LMI imaging using h‐FTAA showed higher retention in the cortex of P301L mice at 10 month‐of‐age compared to age‐matched non‐transgenic littermates. Immunohistochemical staining on P301L mouse brain tissue sections showed co‐localization of h‐FTAA with anti‐phosphorylated tau antibodies AT8 and AT100, thus verifying the specificity of the probe to tauopathy in P301L mice.
Conclusion: We demonstrate a new in vivo high‐resolution imaging platform for detection of tauopathy in murine models of frontal temporal lobe tauopathy.

Abstract

Background: Tau abnormal aggregates have been visualized in‐vivo using intravital microscopy techniques with high resolution, but are limited to a small field‐of‐view and depth. Here, we report a new method for the transcranial detection of tau deposits accross the brain with 6 μm resolution.
Method: In vitro Thioflavin T fluorescence assay was performed to screen fluorescence imaging probes that bind to tau fibrils. P301L (Thy1.2) mouse models of frontal temporal lobe dementia with four repeat tau and non‐transgenic littermates were imaged in vivo using a novel large‐field multifocal illumination (LMI) fluorescence microscopy technique using luminescent conjugated oligothiophenes h‐FTAA. Immunohistochemical staining were performed on P301L mouse brain tissue sections using anti‐phosphorylated tau antibodies AT8 and AT100.
Result: In vitro Thioflavin T fluorescence assay and LMI imaging shows that h‐FTAA bind to recombinant full‐length tau fibrils. In vivo LMI imaging using h‐FTAA showed higher retention in the cortex of P301L mice at 10 month‐of‐age compared to age‐matched non‐transgenic littermates. Immunohistochemical staining on P301L mouse brain tissue sections showed co‐localization of h‐FTAA with anti‐phosphorylated tau antibodies AT8 and AT100, thus verifying the specificity of the probe to tauopathy in P301L mice.
Conclusion: We demonstrate a new in vivo high‐resolution imaging platform for detection of tauopathy in murine models of frontal temporal lobe tauopathy.

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Additional indexing

Item Type:Journal Article, not_refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Pharmacology and Toxicology
07 Faculty of Science > Institute of Pharmacology and Toxicology

04 Faculty of Medicine > Institute of Biomedical Engineering
Dewey Decimal Classification:170 Ethics
610 Medicine & health
Uncontrolled Keywords:Health Policy, Developmental Neuroscience, Epidemiology, Cellular and Molecular Neuroscience, Geriatrics and Gerontology, Psychiatry and Mental health, Clinical Neurology
Language:English
Date:1 December 2020
Deposited On:19 Feb 2021 13:46
Last Modified:22 Feb 2024 09:35
Publisher:Wiley-Blackwell Publishing, Inc.
ISSN:1552-5260
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/alz.047238