Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy
Abstract
BACKGROUND: The translocator protein (TSPO) has been identified as a positron emission tomography (PET)-visible biomarker of inflammation and promising immunotherapeutic target for the treatment of Alzheimer's disease (AD). While TSPO ligands have been shown to reduce the accumulation of the toxic Alzheimer's beta-amyloid peptide, their effect on tau pathology has not yet been investigated. To address this, we analyzed the effects of TSPO ligand, Ro5-4864, on the progression of neuropathology in rTg4510 tau transgenic mice (TauTg). METHODS: Brain atrophy, tau accumulation, and neuroinflammation were assessed longitudinally using volumetric magnetic resonance imaging, tau-PET, and TSPO-PET, respectively. In vivo neuroimaging results were confirmed by immunohistochemistry for markers of neuronal survival (NeuN), tauopathy (AT8), and inflammation (TSPO, ionized calcium-binding adaptor molecule 1 or IBA-1, and complement component 1q or C1q) in brain sections from scanned mice. RESULTS: TSPO ligand treatment attenuated brain atrophy and hippocampal neuronal loss in the absence of any detected effect on tau depositions. Atrophy and neuronal loss were strongly associated with in vivo inflammatory signals measured by TSPO-PET, IBA-1, and levels of C1q, a regulator of the complement cascade. In vitro studies confirmed that the TSPO ligand Ro5-4864 reduces C1q expression in a microglial cell line in response to inflammation, reduction of which has been shown in previous studies to protect synapses and neurons in models of tauopathy. CONCLUSIONS: These findings support a protective role for TSPO ligands in tauopathy, reducing neuroinflammation, neurodegeneration, and brain atrophy.
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BibTeX
@article{fairley2026neuroprotective,
title = {{Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy}},
author = {Lauren H. Fairley and Naruhiko Sahara and Ichio Aoki and Bin Ji and Tetsuya Suhara and Makoto Higuchi and Anna M. Barron},
journal = {Journal of Neuroinflammation},
year = {2026},
month = oct,
doi = {10.1186/s12974-021-02122-1},
url = {https://hal.science/hal-05777678v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Neuroprotective effect of mitochondrial translocator protein ligand in a mouse model of tauopathy
AU - Lauren H. Fairley
AU - Naruhiko Sahara
AU - Ichio Aoki
AU - Bin Ji
AU - Tetsuya Suhara
AU - Makoto Higuchi
AU - Anna M. Barron
PY - 2026
DA - 2026/10/05
JO - Journal of Neuroinflammation
DO - 10.1186/s12974-021-02122-1
UR - https://hal.science/hal-05777678v1
AB - BACKGROUND: The translocator protein (TSPO) has been identified as a positron emission tomography (PET)-visible biomarker of inflammation and promising immunotherapeutic target for the treatment of Alzheimer's disease (AD). While TSPO ligands have been shown to reduce the accumulation of the toxic Alzheimer's beta-amyloid peptide, their effect on tau pathology has not yet been investigated. To address this, we analyzed the effects of TSPO ligand, Ro5-4864, on the progression of neuropathology in rTg4510 tau transgenic mice (TauTg). METHODS: Brain atrophy, tau accumulation, and neuroinflammation were assessed longitudinally using volumetric magnetic resonance imaging, tau-PET, and TSPO-PET, respectively. In vivo neuroimaging results were confirmed by immunohistochemistry for markers of neuronal survival (NeuN), tauopathy (AT8), and inflammation (TSPO, ionized calcium-binding adaptor molecule 1 or IBA-1, and complement component 1q or C1q) in brain sections from scanned mice. RESULTS: TSPO ligand treatment attenuated brain atrophy and hippocampal neuronal loss in the absence of any detected effect on tau depositions. Atrophy and neuronal loss were strongly associated with in vivo inflammatory signals measured by TSPO-PET, IBA-1, and levels of C1q, a regulator of the complement cascade. In vitro studies confirmed that the TSPO ligand Ro5-4864 reduces C1q expression in a microglial cell line in response to inflammation, reduction of which has been shown in previous studies to protect synapses and neurons in models of tauopathy. CONCLUSIONS: These findings support a protective role for TSPO ligands in tauopathy, reducing neuroinflammation, neurodegeneration, and brain atrophy.
SN - 1742-2094
ER -