Angiotensin receptor blockade does not modify tau pathology in line 66 tau-transgenic mice expressing the P301S mutation
- 1School of Medicine, Medical Sciences and Nutrition, University of Aberdeen
Abstract
The aggregation of the microtubule-associated protein tau is a hallmark in many neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Hypertension increases the risk of neurodegenerative diseases, and there is evidence that drugs targeting the renin-angiotensin system (RAS) to reduce blood pressure (BP) could potentially delay neurodegenerative disease onset due to their action on brain RAS. However, the effect of such treatment on pathologies associated with tau are understudied. We have treated three-month old line 66 (L66) tau-transgenic mice expressing the P301S mutation for six weeks with the angiotensin receptor blocker (ARB) candesartan at 5 mg/kg and investigated tau pathology, angiotensin II (Ang II) type 1 receptor (AT1R), Ang II type 2 receptor (AT2R), neurones, microglia, and astrocytes using immunohistochemistry (IHC) and immunoblotting. AT1R and AT2R levels, as well as cortical thickness, number of neurones, GFAP-positive astrocytes and Iba1-positive microglia were all not affected by candesartan treatment. L66 mice had more human tau but less mouse pSer202 tau and total mouse tau, but candesartan treatment did not normalise these differences. Therefore, candesartan administered for six weeks at 5 mg/kg did not lead to a significant reduction of dementia-related pathologies in L66 tau-transgenic mice.
Related
- Early Insulin Signaling Defects and Oxidative Stress Kinase Activation Precede Tau Pathology in PS19 Tau Transgenic Mice
- Chemical and Biological Mobilization of Soil Phosphorus by ppk-Expressing Transgenic Rice (Oryza sativa L.).
- Transgenic Plasmodium berghei expressing P. vivax pre-erythrocytic antigens SSP3 and SPECT1 to elucidate their efficacy towards vaccine development
- C3a receptor signalling in ObRb-expressing neurons promotes leptin resistance and obesity-associated cardiac remodelling
- Alteration of empathy-related behaviors in two strains of mice expressing mutations of the α5 cholinergic nicotinic receptor subunit
BibTeX
@article{schwab2026angiotensin,
title = {{Angiotensin receptor blockade does not modify tau pathology in line 66 tau-transgenic mice expressing the P301S mutation}},
author = {Karima Schwab and Jack Bray and Anne Anschuetz and Ilenia Pinna and Renny Listyono and Valeria Melis and Lianne Robinson and Charles R. Harrington and Gernot Riedel},
journal = {Discover Neuroscience},
year = {2026},
month = nov,
doi = {10.1186/s13064-026-00348-4},
url = {https://doi.org/10.1186/s13064-026-00348-4},
note = {CC BY},
}
RIS
TY - JOUR
TI - Angiotensin receptor blockade does not modify tau pathology in line 66 tau-transgenic mice expressing the P301S mutation
AU - Karima Schwab
AU - Jack Bray
AU - Anne Anschuetz
AU - Ilenia Pinna
AU - Renny Listyono
AU - Valeria Melis
AU - Lianne Robinson
AU - Charles R. Harrington
AU - Gernot Riedel
PY - 2026
DA - 2026/11/08
JO - Discover Neuroscience
DO - 10.1186/s13064-026-00348-4
UR - https://doi.org/10.1186/s13064-026-00348-4
AB - The aggregation of the microtubule-associated protein tau is a hallmark in many neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). Hypertension increases the risk of neurodegenerative diseases, and there is evidence that drugs targeting the renin-angiotensin system (RAS) to reduce blood pressure (BP) could potentially delay neurodegenerative disease onset due to their action on brain RAS. However, the effect of such treatment on pathologies associated with tau are understudied. We have treated three-month old line 66 (L66) tau-transgenic mice expressing the P301S mutation for six weeks with the angiotensin receptor blocker (ARB) candesartan at 5 mg/kg and investigated tau pathology, angiotensin II (Ang II) type 1 receptor (AT1R), Ang II type 2 receptor (AT2R), neurones, microglia, and astrocytes using immunohistochemistry (IHC) and immunoblotting. AT1R and AT2R levels, as well as cortical thickness, number of neurones, GFAP-positive astrocytes and Iba1-positive microglia were all not affected by candesartan treatment. L66 mice had more human tau but less mouse pSer202 tau and total mouse tau, but candesartan treatment did not normalise these differences. Therefore, candesartan administered for six weeks at 5 mg/kg did not lead to a significant reduction of dementia-related pathologies in L66 tau-transgenic mice.
SN - 3005-1827
ER -