BACE1 levels are elevated in congestive heart failure.

Cardiovascular (CV) diseases are known to have a negative impact on the brain and neurocognition, and contribute to the development of vascular dementia and neurodegenerative diseases such as Alzheimer's disease (AD). Among CV diseases, congestive heart failure (CHF) after myocardial infarction (MI) is a condition where the ability of the left ventricle to eject blood to the circulation is impaired. As a consequence, CHF triggers inflammation and results in reduced cerebral blood flow which are considered among the risk factors for development of AD. However, biochemical alterations in the brain following MI and CHF remain unknown. To address this issue, we investigated microglia activation; levels of BACE1, the key rate-limiting enzyme involved in the pathogenesis of AD; and VEGF levels in the hippocampus and cortex following MI. We created MI by the ligation of the left anterior descending coronary artery in Sprague-Dawley male rats and collected brains either 3 days after MI (AMI) or 21 days after MI (CHF). We investigated microglia activation in AMI and CHF brains by immunohistochemistry and immunoblotting using macrophage/microglia marker Ionized calcium binding adaptor molecule 1 (Iba-1), and observed activated morphology of microglia in the cortex of rats in both AMI and CHF. We also showed the levels of BACE1 were increased in the cortex and hippocampus of CHF rats. To determine whether hypoxia occurs in the CHF brain, we assessed levels of VEGF in the hippocampus and cortex. Western blotting analysis showed up-regulation of VEGF in the hippocampus of CHF brains. These results suggest that neuroinflammation takes place secondary to myocardial infarction. In addition, CHF-induced hypoxia might play a role in the elevation of BACE1 and VEGF levels.