Atorvastatin and pitavastatin reduce senile plaques and inflammatory responses in a mouse model of Alzheimer's disease.
OBJECTIVE
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 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-α-positive neurons and the mean total SP area decreased at 15-20 months, compared with APP-Tg mice with vehicle treatment.


CONCLUSIONS
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-α>SPs. 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.
Okayama University, Japan.
Tomoko
T
Kurata
Kazunori
K
Miyazaki
Miki
M
Kozuki
Nobutoshi
N
Morimoto
Yasuyuki
Y
Ohta
Yoshio
Y
Ikeda
Koji
K
Abe
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000378:metabolism / Q000473:pathology*; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D000069059:Atorvastatin; C108475:pitavastatin