Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line

Proc Natl Acad Sci U S A. 1995 Oct 10;92(21):9480-4. doi: 10.1073/pnas.92.21.9480.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apolipoprotein E3
  • Apolipoproteins E / metabolism*
  • Carbocyanines
  • Cell Line
  • Cross-Linking Reagents
  • Fluorescent Antibody Technique, Indirect
  • Fluorescent Dyes
  • Hypothalamus / cytology
  • Hypothalamus / physiology*
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Neurites / physiology*
  • Neurites / ultrastructure
  • Neurons / cytology
  • Neurons / physiology
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism*
  • Receptors, LDL / metabolism*
  • Recombinant Proteins / immunology
  • Recombinant Proteins / metabolism


  • Apolipoprotein E3
  • Apolipoproteins E
  • Carbocyanines
  • Cross-Linking Reagents
  • Fluorescent Dyes
  • Low Density Lipoprotein Receptor-Related Protein-1
  • Receptors, Immunologic
  • Receptors, LDL
  • Recombinant Proteins
  • 3,3'-dioctadecylindocarbocyanine