Wiesmann, Maximilian;
Roelofs, Monica;
van der Lugt, Robert;
Heerschap, Arend;
Kiliaan, Amanda J;
Claassen, Jurgen AHR
Angiotensin II, hypertension and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer's disease
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Media type:
E-Article
Title:
Angiotensin II, hypertension and angiotensin II receptor antagonism: Roles in the behavioural and brain pathology of a mouse model of Alzheimer's disease
Contributor:
Wiesmann, Maximilian;
Roelofs, Monica;
van der Lugt, Robert;
Heerschap, Arend;
Kiliaan, Amanda J;
Claassen, Jurgen AHR
Published:
SAGE Publications, 2017
Published in:
Journal of Cerebral Blood Flow & Metabolism, 37 (2017) 7, Seite 2396-2413
Language:
English
DOI:
10.1177/0271678x16667364
ISSN:
0271-678X;
1559-7016
Origination:
Footnote:
Description:
Elevated angiotensin II causes hypertension and contributes to Alzheimer’s disease by affecting cerebral blood flow. Angiotensin II receptor blockers may provide candidates to reduce (vascular) risk factors for Alzheimer’s disease. We studied effects of two months of angiotensin II-induced hypertension on systolic blood pressure, and treatment with the angiotensin II receptor blockers, eprosartan mesylate, after one month of induced hypertension in wild-type C57bl/6j and AβPPswe/PS1ΔE9 (AβPP/PS1/Alzheimer’s disease) mice. AβPP/PS1 showed higher systolic blood pressure than wild-type. Subsequent eprosartan mesylate treatment restored this elevated systolic blood pressure in all mice. Functional connectivity was decreased in angiotensin II-infused Alzheimer’s disease and wild-type mice, and only 12 months of Alzheimer’s disease mice showed impaired cerebral blood flow. Only angiotensin II-infused Alzheimer’s disease mice exhibited decreased spatial learning in the Morris water maze. Altogether, angiotensin II-induced hypertension not only exacerbated Alzheimer’s disease-like pathological changes such as impairment of cerebral blood flow, functional connectivity, and cognition only in Alzheimer’s disease model mice, but it also induced decreased functional connectivity in wild-type mice. However, we could not detect hypertension-induced overexpression of Aβ nor increased neuroinflammation. Our findings suggest a link between midlife hypertension, decreased cerebral hemodynamics and connectivity in an Alzheimer’s disease mouse model. Eprosartan mesylate treatment restored and beneficially affected cerebral blood flow and connectivity. This model could be used to investigate prevention/treatment strategies in early Alzheimer’s disease.