Role of apolipoprotein E in the molecular pathomechanism of Alzheimer disease

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 epsilon 4 allele are at increased risk of Alzheimer disease (AD) compared with those carrying the more common epsilon 3 allele, whereas the epsilon 2 allele decreases risk. ApoE-HDL binds to several cell-surface receptors to deliver lipids, and also to amyloid-beta (A beta) proteins. A beta 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 A beta 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 A beta with different ApoE isoforms.