The effect of Alzheimer’s disease drugs on excessive bleeding

Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), is an enzyme that promotes the production of amyloid-beta (Aβ) peptides in the brain, a key factor in the development of Alzheimer's disease. Recent publications have demonstrated that BACE1 may also directly modulate interleukin (IL)-6 signalling, an important cytokine in effecting activation of blood platelets. However, the effects of BACE1 on platelet-dependent mechanisms, such as blood clotting and thrombosis, remain to be investigated. The student will aim to determine whether BACE1 is important for coagulation, thrombosis or thrombolysis, testing the effect of BACE1 knockout mice and the effect of drug inhibitors of BACE1 on murine and human whole blood clotting. The project will employ a number of techniques including whole blood rotational thromboelastometry (ROTEM) and turbidimetric plasma analysis for the measurement of differences in clot formation. In addition, flow-cytometry analysis of platelet markers, and platelet aggregation techniques, will be used to directly investigate the effect of BACE1 on platelets. The student will be trained and routinely supervised by Leander within the group of Cedric Duval. Students will need to find their own accommodation and be expected to present their findings orally at a research day in York on 08th September 2026.