Possible link between lipid metabolism and cerebral amyloid angiopathy in Alzheimer's disease: A role for high-density lipoproteins?

Although apolipoprotein E4 (ApoE4) is a well-established risk factor for th e development of Alzheimer's disease (AD), it is unclear how ApoE affects t he progression of the disease. beta-amyloid (A beta) is a major constituent of cerebrovascular amyloid deposits in brains of subjects with Alzheimer's disease. In cerebrospinal fluid and in plasma, A beta 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 in teraction with ApoE and heparan sulphate proteoglycans (HSPG) in the subend othelial space of cerebral microvessels. At the same time, HDL may have a r ole in maintaining A beta soluble and in mediating its clearance. Therefore , similar factors, e.g. HDL, ApoE and HSPG, may be involved in the regulati on of reverse cholesterol transport in the brain and in the processing of A beta. Alterations in the process of cholesterol secretion from the brain m ay contribute to the deposition of A beta in the vascular wall.