Role of apoE in late-onset Alzheimer’s and cardiovascular disease
One of the major risk factors associated with cardiovascular and Alzheimer's disease is apolipopprotein E (apoE). ApoE exists as three major isoforms that differ due to single amino acid substitutions at positions 112 and 158. ApoE3 (112C158R) is the most common isoform and is associated with a healthy state; whereas apoE2 (112C158C) and apoE4 (112R158R) are strongly linked to an increased risk of developing type III hyperlipoproteinemia and late-onset Alzheimer's disease, respectively.
This project aims to compare the structure, function and protein-protein interaction networks of apoE isoforms using analytical ultracentrifugation, isothermal titration microcalorimetry, lipid binding assays, mass spectrometry, microscale thermophoresis, molecular dynamics simulations (in collaboration with Dr Matthew Downton and Dr John Wagner from IBM) and X-ray crystallography (in collaboration with Dr Luke Miles and Prof Michael Parker from St Vincent's Institute of Medical Research).