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Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice

The cell-to-cell transmission of tau aggregates is considered a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer’s disease (AD) and other tauopathies. Recent studies suggest that tau oligomers, rather than fibrils, participate in this process. We previously showed that...

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Autores principales: Umeda, Tomohiro, Uekado, Rumi, Shigemori, Keiko, Eguchi, Hiroshi, Tomiyama, Takami
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869211/
https://www.ncbi.nlm.nih.gov/pubmed/35203506
http://dx.doi.org/10.3390/biomedicines10020297
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author Umeda, Tomohiro
Uekado, Rumi
Shigemori, Keiko
Eguchi, Hiroshi
Tomiyama, Takami
author_facet Umeda, Tomohiro
Uekado, Rumi
Shigemori, Keiko
Eguchi, Hiroshi
Tomiyama, Takami
author_sort Umeda, Tomohiro
collection PubMed
description The cell-to-cell transmission of tau aggregates is considered a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer’s disease (AD) and other tauopathies. Recent studies suggest that tau oligomers, rather than fibrils, participate in this process. We previously showed that intranasal rifampicin inhibits tau oligomer accumulation and improves cognition in tauopathy mice. In the present study, we examined the effects of nasal rifampicin on tau propagation in a new mouse model of tauopathy. A tau oligomer-rich fraction prepared from the brain of an AD patient was injected into a unilateral hippocampus of tau264 mice that express both 3-repeat and 4-repeat wild-type human tau. Rifampicin administration was started one week after the injection and performed three times a week for 24 weeks. Cognitive function and tau pathology were assessed by the Morris water maze test and brain section staining. Rifampicin treatment inhibited the spreading of tau oligomers from the injection site to other brain regions and neurofibrillary tangle formation in the entorhinal cortex. Synapse and neuronal loss in the hippocampus were also prevented, and cognitive function remained normal. These results suggest that intranasal rifampicin could be a promising remedy that halts the progression of tauopathy by inhibiting tau oligomer propagation.
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spelling pubmed-88692112022-02-25 Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice Umeda, Tomohiro Uekado, Rumi Shigemori, Keiko Eguchi, Hiroshi Tomiyama, Takami Biomedicines Article The cell-to-cell transmission of tau aggregates is considered a mechanism underlying the intracerebral spreading of tau pathology in Alzheimer’s disease (AD) and other tauopathies. Recent studies suggest that tau oligomers, rather than fibrils, participate in this process. We previously showed that intranasal rifampicin inhibits tau oligomer accumulation and improves cognition in tauopathy mice. In the present study, we examined the effects of nasal rifampicin on tau propagation in a new mouse model of tauopathy. A tau oligomer-rich fraction prepared from the brain of an AD patient was injected into a unilateral hippocampus of tau264 mice that express both 3-repeat and 4-repeat wild-type human tau. Rifampicin administration was started one week after the injection and performed three times a week for 24 weeks. Cognitive function and tau pathology were assessed by the Morris water maze test and brain section staining. Rifampicin treatment inhibited the spreading of tau oligomers from the injection site to other brain regions and neurofibrillary tangle formation in the entorhinal cortex. Synapse and neuronal loss in the hippocampus were also prevented, and cognitive function remained normal. These results suggest that intranasal rifampicin could be a promising remedy that halts the progression of tauopathy by inhibiting tau oligomer propagation. MDPI 2022-01-27 /pmc/articles/PMC8869211/ /pubmed/35203506 http://dx.doi.org/10.3390/biomedicines10020297 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Umeda, Tomohiro
Uekado, Rumi
Shigemori, Keiko
Eguchi, Hiroshi
Tomiyama, Takami
Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
title Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
title_full Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
title_fullStr Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
title_full_unstemmed Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
title_short Nasal Rifampicin Halts the Progression of Tauopathy by Inhibiting Tau Oligomer Propagation in Alzheimer Brain Extract-Injected Mice
title_sort nasal rifampicin halts the progression of tauopathy by inhibiting tau oligomer propagation in alzheimer brain extract-injected mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869211/
https://www.ncbi.nlm.nih.gov/pubmed/35203506
http://dx.doi.org/10.3390/biomedicines10020297
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