Reuter, Björn, Venus, A, Grudenski, S, Heiler, P, Schad, L, Staufenbiel, Matthias, Hennerici, G and Fatar, M (2016) Statin therapy and the development of cerebral amyloid angiopathy – a rodent in-vivo approach. Int. J. Mol. Sci..

Abstract

Background
Cerebral amyloid angiopathy (CAA) is characterized by vascular deposition of amyloid β (Aβ) with a higher incidence of lobar cerebral microbleeds (cMBs) and spontaneous hemorrhage. Up to now no specific therapy is available. Since statins are well known for their effects in vascular and potentially neurodegenerative disorders we tested for the effect on CAA and cMBs.
Methods
APP23-transgenic (tg) mice received atorvastatin-supplemented food starting at the age of 8 months (n=13), 12 months (n=7) and 16 months (n=6), respectively. The control group (n=16) received standard food only. At the age of 24 months cMBs were determined in T2* weighted images obtained by 9.4 T magnetic resonance imaging (MRI) and graded by size. Additionally cMBs and numbers/severity of Aβ affected vessels were assessed histologically in a subgroup of mice treated for 16 months (n=7) and controls (n=6).
Results
Mean cMB number was not significantly changed by treatment and treatment time. Control mice displayed an average of 35±18.5 cMBs, compared to 29.3±9.8 in mice with 8 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), respectively. In a 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). In histology assessed numbers of cMBs were comparable to MRI data. Mean number of Aβ affected vessels per mouse and the calculated CAA-severity score tended to be lower after Statin treatment (120±20.1 vs. 138.3±25.7, p=0.18 and 228.1±54.5 vs. 271.3±36, p=0.13).
Conclusion
Despite to a non-significant trend towards fewer vascular Aβ deposits and cMBs our results failed to provide evidence for beneficial effects of long term atorvastatin treatment in the APP23-tg mouse model of CAA. A higher risk for bleeding complications under long term statin therapy in CAA was not observed in this model.

Item Type:	Article
Keywords:	CAA, transgenic mice, APP23, statins, microbleeds, amyloid
Date Deposited:	04 May 2016 23:45
Last Modified:	04 May 2016 23:45
URI:	https://oak.novartis.com/id/eprint/25859