Although apolipoprotein E4 (ApoE4) is a well-established risk factor for the development of Alzheimer's disease (AD), it is unclear how ApoE affects the progression of the disease. beta-amyloid (Abeta) is a major constituent of cerebrovascular amyloid deposits in brains of subjects with Alzheimer's disease. In cerebrospinal fluid and in plasma, Abeta is normally present in association with high density lipoproteins (HDL). These lipoproteins may play a role in the removal of excess cholesterol from the brain through interaction with ApoE and heparan sulphate proteoglycans (HSPG) in the subendothelial space of cerebral microvessels. At the same time, HDL may have a role in maintaining Abeta soluble and in mediating its clearance. Therefore, similar factors, e.g. HDL, ApoE and HSPG, may be involved in the regulation of reverse cholesterol transport in the brain and in the processing of Abeta. Alterations in the process of cholesterol secretion from the brain may contribute to the deposition of Abeta in the vascular wall.