2008/12/23 by Robert W. Mahley, Karl H. Weisgraber, Yadong Huang · 5 citations
Medicine · Neuroscience · #Alzheimer's disease research and treatments #Lipoproteins and Cardiovascular Health #Diabetes, Cardiovascular Risks, and Lipoproteins #Apolipoprotein E #Disease #Pathological #Genetic predisposition #Apolipoprotein B #Biology #Lipoprotein #Allele #Risk factor #Receptor #Stressor #Mechanism (biology) #Alzheimer's disease #Host factor #Immunology #Medicine #Genetics #Internal medicine #Cholesterol #Neuroscience #Gene #Virus #Endocrinology
paper · pdf · doi:10.1194/jlr.r800069-jlr200
openalex publication_date 2008/12/23 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/29
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. 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.