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

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.