Abstract

is critical for lipid transport and cholesterol homeostasis in the central nervous system and plasma and is involved in neuronal plasticity ( 3). ApoE has three common iso-forms (apoE2, apoE3, and apoE4) distinguished by cyste-ine/arginine content, and each form has different effects on plasma cholesterol levels ( 4). ApoE4 is associated with the highest plasma cholesterol and low density lipoprotein (LDL) concentrations and is thus associated with an in-creased risk for cardiovascular disease ( 5, 6), and is also the major genetic risk factor for sporadic, late-onset Alz-heimer’s disease ( 7–10). To understand the mechanisms of biologically active apoE, its structure must be unraveled. The crystal struc-ture of apoE in the lipid-free state shows that the N-termi-nal domain is a globular four-helix bundle ( 11). In the