However, while elevated Aβ levels may facilitate positive feedback loop whereby increased Aβ facilitates enhanced BACE1 activity and auto-potentiates its own production, there is accumulating data which links several well-established AD risk factors (cardiovascular diseases, stroke, ischemia and TBI), and their associated molecular changes (hypoperfusion, hypoxia, metabolic dysfunction, energy inhibition and oxidative stress), with increases in BACE1. Here, BACE1 is linked to ischemia.