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

David M. Holtzman, Robert E. Pitas, Joshua Kilbridge, Britto Nathan, Robert W. Mahley, Guojun D Bu, Alan L. Schwartz

Research output: Contribution to journalArticle

315 Citations (Scopus)

Abstract

The ε4 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.

Original languageEnglish (US)
Pages (from-to)9480-9484
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number21
DOIs
StatePublished - Oct 10 1995
Externally publishedYes

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LDL-Receptor Related Proteins
Apolipoprotein E3
LDL Receptors
Apolipoproteins E
Lipoprotein Receptors
Apolipoprotein E4
Central Nervous System
Neurites
Cell Line
Alzheimer Disease
Protein Isoforms
Low Density Lipoprotein Receptor-Related Protein-1
Biological Phenomena
Neurons
Proteins
Lipoproteins
Alleles
Ligands
Antibodies
Brain

ASJC Scopus subject areas

  • General
  • Genetics

Cite this

Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line. / Holtzman, David M.; Pitas, Robert E.; Kilbridge, Joshua; Nathan, Britto; Mahley, Robert W.; Bu, Guojun D; Schwartz, Alan L.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 92, No. 21, 10.10.1995, p. 9480-9484.

Research output: Contribution to journalArticle

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