title: Statin Therapy and the Development of Cerebral Amyloid Angiopathy--A Rodent in Vivo Approach.
abstract: BACKGROUND
  Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of cerebral microbleeds (cMBs) and spontaneous hemorrhage. Since statins are known for their benefit in vascular disease we tested for the effect on CAA.
  
  
  METHODS
  APP23-transgenic mice received atorvastatin-supplemented food starting at the age of eight months (n = 13), 12 months (n = 7), and 16 months (n = 6), respectively. Controls (n = 16) received standard food only. At 24 months of age cMBs were determined with T2*-weighted 9.4T magnetic resonance imaging and graded by size.
  
  
  RESULTS
  Control mice displayed an average of 35 ± 18.5 cMBs (mean ± standard deviation), compared to 29.3 ± 9.8 in mice with eight months (p = 0.49), 24.9 ± 21.3 with 12 months (p = 0.26), and 27.8 ± 15.4 with 16 months of atorvastatin treatment (p = 0.27). In combined analysis treated mice showed lower absolute numbers (27.4 ± 15.6, p = 0.16) compared to controls and also after adjustment for cMB size (p = 0.13).
  
  
  CONCLUSIONS
  Despite to a non-significant trend towards fewer cMBs our results failed to provide evidence for beneficial effects of long-term atorvastatin treatment in the APP23-transgenic mouse model of CAA. A higher risk for bleeding complications was not observed.
authors.affiliation: Department of Neurology and Neurophysiology, University Freiburg, 79106 Freiburg, Germany. bjoern.reuter@uniklinik-freiburg.de.
authors.forename: Björn
authors.initials: B
authors.lastname: Reuter
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, 68167 Mannheim, Germany. venus.alexander@gmx.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Venus
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, 68167 Mannheim, Germany. grudzenski@neuro.ma.uni-heidelberg.de.
authors.forename: Saskia
authors.initials: S
authors.lastname: Grudzenski
authors.affiliation: Computer Assisted Clinical Medicine, Heidelberg University, 68167 Mannheim, Germany. patrick.heiler@siemens.com.
authors.forename: Patrick
authors.initials: P
authors.lastname: Heiler
authors.affiliation: Computer Assisted Clinical Medicine, Heidelberg University, 68167 Mannheim, Germany. lothar.schad@medma.uni-heidelberg.de.
authors.forename: Lothar
authors.initials: L
authors.lastname: Schad
authors.affiliation: Nervous System Department, Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland. staufenbiel.m@gmail.com.
authors.forename: Matthias
authors.initials: M
authors.lastname: Staufenbiel
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, 68167 Mannheim, Germany. m.g.hennerici@eurostroke.eu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Hennerici
authors.affiliation: Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, 68167 Mannheim, Germany. fatar@neuro.ma.uni-heidelberg.de.
authors.forename: Marc
authors.initials: M
authors.lastname: Fatar
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology*; D016657:Cerebral Amyloid Angiopathy / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic
chemical_list: D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D000069059:Atorvastatin
keywords: APP23; CAA; amyloid; cerebral microbleeds; statins; transgenic mice