Detrimental Effects of Centrally Administered Angiotensin II are Enhanced in a Mouse Model of Alzheimer Disease Independently of Blood Pressure

Abstract

Background The significance of brain angiotensin II in Alzheimer disease ( AD ) is unclear. Methods and Results To examine the role of brain angiotensin II in AD , intracerebroventricular angiotensin II infusion was performed on 5 XFAD mice, a mouse model of AD , and wild‐type mice, and the detrimental effects of brain angiotensin II was compared between the 2 strains of mice. Intracerebroventricular angiotensin II infusion significantly impaired cognitive function in 5 XFAD mice but not in wild‐type mice. This vulnerability of 5 XFAD mice to brain angiotensin II was associated with enhancement of hippocampal inflammation and oxidative stress and with increased cerebrovascular amyloid β deposition. We also compared the effect of brain angiotensin II on the heart and skeletal muscle between the 2 strains because AD is associated with heart failure and sarcopenia. We found that cardiac compensatory response of 5 XFAD mice to brain angiotensin II –induced hypertension was less than that of wild‐type mice. Brain angiotensin II caused skeletal muscle atrophy and injury in 5 XFAD mice more than in wild‐type mice. Conclusions Brain angiotensin II seems to be involved in cognitive impairment and brain injury in AD , which is associated with oxidative stress, inflammation, and cerebral amyloid angiopathy. Further, brain angiotensin II may participate in cardiac disease and sarcopenia observed in AD .