Journal
JOURNAL OF LIPID RESEARCH
Volume 50, Issue -, Pages S183-S188Publisher
ELSEVIER
DOI: 10.1194/jlr.R800069-JLR200
Keywords
cholesterol; neurodegeneration; HIV; coronary heart disease; LDL receptor; dysbetalipoproteinemia; heparan sulfate proteoglycans; infectious diseases; evolution
Categories
Funding
- National Institutes of Health [R01 AG028793, 2P01AG02207]
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Apolipoprotein (apo) E has roles beyond lipoprotein metabolism. The detrimental effects of apoE4 in cardiovascular, neurological, and infectious diseases correlate with its structural features (e.g., domain interaction) that distinguish it from apoE3 and apoE2. Structure/function studies revealed that apoE2 is severely defective in LDL receptor binding because of a structural difference that alters the receptor binding region and helped unravel the mechanism of type III hyperlipoproteinemia. ApoE4 is the major genetic risk factor for Alzheimer's disease and sets the stage for neuropathological disorders precipitated by genetic, metabolic, and environmental stressors. ApoE also influences susceptibility to parasitic, bacterial, and viral infections. In HIV-positive patients, apoE4 homozygosity hastens progression to AIDS and death and increases susceptibility to opportunistic infections. jlr The next phase in our understanding of apoE will be characterized by clinical intervention to prevent or reverse the detrimental effects of apoE4 by modulating its structure or blocking the pathological processes it mediates.-Mahley, R. W., K. H. Weisgraber, and Y. Huang. Apolipoprotein E: structure determines function, from atherosclerosis to Alzheimer's disease to AIDS. J. Lipid Res. 2009. S183-S188.
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