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Int. J. Mol. Sci. 2016, 17(1), 126; doi:10.3390/ijms17010126

Statin Therapy and the Development of Cerebral Amyloid Angiopathy—A Rodent in Vivo Approach

1
Department of Neurology and Neurophysiology, University Freiburg, 79106 Freiburg, Germany
2
Department of Neurology, Universitätsmedizin Mannheim, Heidelberg University, 68167 Mannheim, Germany
3
Computer Assisted Clinical Medicine, Heidelberg University, 68167 Mannheim, Germany
4
Nervous System Department, Novartis Institutes for Biomedical Research, 4002 Basel, Switzerland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Amal Kaddoumi
Received: 16 December 2015 / Revised: 4 January 2016 / Accepted: 12 January 2016 / Published: 19 January 2016
(This article belongs to the Special Issue Amyloid-beta and Neurological Diseases)
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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). Conclusion: 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. View Full-Text
Keywords: CAA; transgenic mice; APP23; statins; cerebral microbleeds; amyloid CAA; transgenic mice; APP23; statins; cerebral microbleeds; amyloid
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MDPI and ACS Style

Reuter, B.; Venus, A.; Grudzenski, S.; Heiler, P.; Schad, L.; Staufenbiel, M.; Hennerici, M.G.; Fatar, M. Statin Therapy and the Development of Cerebral Amyloid Angiopathy—A Rodent in Vivo Approach. Int. J. Mol. Sci. 2016, 17, 126.

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