Dysregulation of SREBP2 induces BACE1 expression

► We propose a link between alterations of brain cholesterol homeostasis and BACE1. ► We utilized high-fat fed rats and high cholesterol-treated SK-N-BE cells. ► In both models we observed an increased expression of SREBP2 and BACE1. ► SREBP2 is able to bind BACE1 promoter and directly induce its expression. ► Changes in brain cholesterol represent a risk for BACE1 activation.