title: Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.
abstract: The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence neurons in the aging brain. Recent data suggest that apoE-containing lipoproteins can influence neurite outgrowth in an isoform-specific fashion. The neuronal mediators of apoE effects have not been clarified. We show here that in a central nervous system-derived neuronal cell line, apoE3 but not apoE4 increases neurite extension. The effect of apoE3 was blocked at low nanomolar concentrations by purified 39-kDa protein that regulates ligand binding to the low density lipoprotein receptor-related protein (LRP). Anti-LRP antibody also completely abolished the neurite-promoting effect of apoE3. Understanding isoform-specific cell biological processes mediated by apoE-LRP interactions in central nervous system neurons may provide insight into Alzheimer disease pathogenesis.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: D M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: R E
authors.initials: RE
authors.lastname: Pitas
authors.forename: J
authors.initials: J
authors.lastname: Kilbridge
authors.forename: B
authors.initials: B
authors.lastname: Nathan
authors.forename: R W
authors.initials: RW
authors.lastname: Mahley
authors.forename: G
authors.initials: G
authors.lastname: Bu
authors.forename: A L
authors.initials: AL
authors.lastname: Schwartz
mesh_terms: D053318:Apolipoprotein E3; D001057:Apolipoproteins E / Q000378:metabolism*; D002232:Carbocyanines; D002460:Cell Line; D003432:Cross-Linking Reagents; D019084:Fluorescent Antibody Technique, Indirect; D005456:Fluorescent Dyes; D007031:Hypothalamus / Q000166:cytology / Q000502:physiology*; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011973:Receptors, LDL / Q000378:metabolism*; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D053318:Apolipoprotein E3; D001057:Apolipoproteins E; D002232:Carbocyanines; D003432:Cross-Linking Reagents; D005456:Fluorescent Dyes; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D011994:Recombinant Proteins; C024286:3,3'-dioctadecylindocarbocyanine