The role of BACE1 in cardiovascular health and disease

Brain deposits of a peptide called Abeta are a characteristic hallmark of Alzheimer’s disease (AD). BACE1 is the main enzyme responsible for Abeta production and thus AD development and is a current therapeutic target for AD. We have shown that inhibiting BACE1 reduces obesity and diabetes in mice by improving insulin and leptin actions. There is also a strong link between Cardiovascular disease (CVD) and AD risk. Indeed these diseases have etiology in common including oxidative and inflammatory stress and insulin and/or leptin resistance. Importantly, little is known regarding BACE1-Abeta impact on CVD. This project aims to determine whether BACE1 levels and activity correlate with CV function measures and if reduction in BACE1 activity can improve CV function in obese mice. If true BACE1 levels and/or activity could be a potential biomarker for CVD risk or target for new drug development.