[Role of apolipoprotein E in the molecular pathomechanism of Alzheimer disease].

Abstract

Apolipoprotein E (Apo-E) is a major cholesterol carrier regulating lipid transport and injury repair in the brain. It is known that individuals carrying the epsilon4 allele are at increased risk of Alzheimer disease (AD) compared with those carrying the more common epsilon3 allele, whereas the epsilon2 allele decreases risk. ApoE-HDL binds to several cell-surface receptors to deliver lipids, and also to amyloid-beta (Abeta) proteins. Abeta is thought to initiate toxic events that lead to synaptic dysfunction and neurodegeneration in AD. It has been shown that Apo-E isoforms differentially regulate Abeta aggregation and clearance in the brain, and have distinct functions in regulating brain lipid transport, and mitochondrial function. In this review, we summarize current knowledge about Apo-E in the CNS, with a particular emphasis on its functions to generate HDL and clear/degradate of HDL-bound Abeta with different ApoE isoforms.