title: Atorvastatin and pitavastatin reduce oxidative stress and improve IR/LDL-R signals in Alzheimer's disease.
abstract: OBJECTIVE
  To examine and compare the pleiotropic effects on oxidative stress and metabolic signaling pathways of atorvastatin and pitavastatin in mouse model of Alzheimer's disease (AD).
  
  
  METHODS
  We gave the transgenic (Tg) mice either atorvastatin or pitavastatin from 5-20 months (M) of age, and performed immunohistological analysis [4-hydroxy-2-nonenal (4-HNE)-positive, advanced glycation end products (AGEs), low-density lipoprotein receptor (LDL-R)-positive neurons, apolipoprotein E (ApoE)-positive senile plaque (SP), and insulin receptor (IR)-positive endothelium], and biochemistry analysis (adiponectin and leptin).
  
  
  RESULTS
  The numbers of 4-HNE- and AGE-positive neurons and the sum of ApoE-positive SP size progressively increased with age in amyloid precursor protein (APP)-Tg mice, while the amount of IR-positive endothelium and the number of LDL-R-positive neurons decreased. Adiponectin and leptin serum levels were lower in APP-Tg mice than in non-Tg mice. Treatment with statins reduced the number of AGE-positive neurons from as early as 10 M, preserved the numbers of 4-HNE- and LDL-R-positive neurons and the amount of IR-positive endothelium at 15 M, and reduced the sum of ApoE-positive SP size and adiponectin serum level at 20 M.
  
  
  CONCLUSIONS
  Atorvastatin and pitavastatin reduced the level of oxidative stress, as revealed by the presence of 4-HNE and AGE, in AD mouse brains, and that treatment with statins improves insulin signaling and LDL-R/ApoE systems. The beneficial effects of these statins may be associated with direct pleiotropic effects on AD mouse brains, indirect effects through improving the serum adiponectin/leptin balance, or both.
authors: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
authors: Tomoko
authors: T
authors: Kurata
authors: Kazunori
authors: K
authors: Miyazaki
authors: Nobutoshi
authors: N
authors: Morimoto
authors: Hiromi
authors: H
authors: Kawai
authors: Yasuyuki
authors: Y
authors: Ohta
authors: Yoshio
authors: Y
authors: Ikeda
authors: Koji
authors: K
authors: Abe
mesh_terms: D052242:Adiponectin / Q000097:blood; D000544:Alzheimer Disease / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D000069059:Atorvastatin; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D020738:Leptin / Q000097:blood; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D058225:Plaque, Amyloid / Q000188:drug therapy; D011758:Pyrroles / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D011972:Receptor, Insulin / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D052242:Adiponectin; D016564:Amyloid beta-Protein Precursor; D017127:Glycation End Products, Advanced; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D020738:Leptin; D011758:Pyrroles; D011804:Quinolines; D011973:Receptors, LDL; D000069059:Atorvastatin; D011972:Receptor, Insulin; C108475:pitavastatin