Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer's disease

Tomoko Kurata, Kazunori Miyazaki, Miki Kozuki, Nobutoshi Morimoto, Yasuyuki Ohta, Yoshio Ikeda, Koji Abe

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Objectives: To examine and compare the pleiotropic anti-inflammatory effects and the long-term effects of atorvastatin and pitavasatin in mouse model of Alzheimer's disease (AD). Methods: We examined the effects of two strong statins on senile plaque (SP) size and inflammatory responses in the brain of an amyloid precursor protein (APP) transgenic (Tg) mouse. We gave the Tg mice either atorvastatin or pitavastatin from 5-20 months of age, and performed immunohistological analysis [SP area, monocyte chemotactic protein 1 (MCP-1)-positive neurons, ionized calcium-binding adaptor molecule 1 (Iba-1)-1-positive microglia, and tumor necrosis factor α (TNF-α)-positive neurons] every d 5 months. Results: In the APP-Tg mice treated with both statins, the number of MCP-1-positive neurons was reduced at 10 months, that of Iba-1-positive microglia was reduced at 15 months, and that of TNF-a-positive neurons and the mean total SP area decreased at 15-20 months, compared with APP-Tg mice with vehicle treatment. Discussion: The protective effect of these statins took 5 months to reach significance in these mice, and the order of sensitivity to statin treatment was MCP-1>Iba-1>TNF-αSPs. Proinflammatory responses including MCP-1, Iba-1, and TNF-α preceded and possibly contributed to SP formation. Pitavastatin has the same significant pleiotrophic effect to prevent and ameliorate inflammation and also has a long-term effect compared with atorvastatin, and both of them have high potential for a preventative approach in patients at risk of AD.

Original languageEnglish
Pages (from-to)601-610
Number of pages10
JournalNeurological Research
Volume34
Issue number6
DOIs
Publication statusPublished - Jul 2012

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Chemokine CCL2
Amyloid Plaques
Transgenic Mice
Amyloid beta-Protein Precursor
Alzheimer Disease
Tumor Necrosis Factor-alpha
Calcium
Neurons
Microglia
Anti-Inflammatory Agents
Inflammation
pitavastatin
Atorvastatin Calcium
Brain
Therapeutics

Keywords

  • Alzheimer's disease
  • Atorvastatin
  • Inflammation
  • Pitavastatin
  • Transgenic mouse

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer's disease. / Kurata, Tomoko; Miyazaki, Kazunori; Kozuki, Miki; Morimoto, Nobutoshi; Ohta, Yasuyuki; Ikeda, Yoshio; Abe, Koji.

In: Neurological Research, Vol. 34, No. 6, 07.2012, p. 601-610.

Research output: Contribution to journalArticle

Kurata, Tomoko ; Miyazaki, Kazunori ; Kozuki, Miki ; Morimoto, Nobutoshi ; Ohta, Yasuyuki ; Ikeda, Yoshio ; Abe, Koji. / Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer's disease. In: Neurological Research. 2012 ; Vol. 34, No. 6. pp. 601-610.
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