Long-term Effect of Telmisartan on Alzheimer's Amyloid Genesis in SHR-SR After tMCAO

Tomoko Kurata, Violeta Lukic, Miki Kozuki, Daisuke Wada, Kazunori Miyazaki, Nobutoshi Morimoto, Yasuyuki Ohta, Kentaro Deguchi, Toru Yamashita, Nozomi Hishikawa, Kosuke Matsuzono, Yoshio Ikeda, Tatsushi Kamiya, Koji Abe

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12 Citations (Scopus)

Abstract

Telmisartan is expected to reduce not only the level of blood pressure but also neuroinflammation and neurotoxicity via pleiotrophic effects as a metabo-sartan. We examined the effects of telmisartan on Alzheimer's disease (AD) pathology in spontaneously hypertensive rat stroke resistant (SHR-SR) after transient middle cerebral artery occlusion (tMCAO) by giving either telmisartan at 0 (vehicle), 0.3 mg/kg/day (low dose, with no reduction of blood pressure), or 3 mg/kg/day (high dose, with a significant reduction of blood pressure) p.o. from 3 months (M) of age, and performed immunohistological analysis at 6, 12, and 18 M of age. The numbers of amyloid β (Aβ)-positive neurons in the cerebral cortex and hippocampus and senile plaque (SP) in the ipsilateral cerebral cortex progressively increased with age until 18 M in the SHR-SR after tMCAO. On the other hand, low-dose telmisartan significantly reduced the number of Aβ-positive neuron as well as SP at 6, 12, and 18 M. High-dose telmisartan showed further reductions of the above AD pathology. The present study suggests that telmisartan reduced both intracellular Aβ and extracellular SP accumulations after tMCAO in SHR-SR, with a further improvement by combined BP lowering. Such a strong effect of telmisartan could provide a preventative approach for AD in post-stroke patients with hypertension.

Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalTranslational Stroke Research
DOIs
Publication statusAccepted/In press - 2014

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Keywords

  • Alzheimer's disease
  • Amyloid β, Metabolic syndrome
  • Spontaneously hypertensive rat
  • Telmisartan
  • Transient middle cerebral artery occlusion

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

Cite this

Kurata, T., Lukic, V., Kozuki, M., Wada, D., Miyazaki, K., Morimoto, N., Ohta, Y., Deguchi, K., Yamashita, T., Hishikawa, N., Matsuzono, K., Ikeda, Y., Kamiya, T., & Abe, K. (Accepted/In press). Long-term Effect of Telmisartan on Alzheimer's Amyloid Genesis in SHR-SR After tMCAO. Translational Stroke Research, 1-9. https://doi.org/10.1007/s12975-013-0321-y