Low density lipoprotein receptor-related protein mediates apolipoprotein E-dependent neurite outgrowth in a central nervous system-derived neuronal cell line.
DM Holtzman, RE Pitas, J Kilbridge… - Proceedings of the …, 1995 - National Acad Sciences
DM Holtzman, RE Pitas, J Kilbridge, B Nathan, RW Mahley, G Bu, AL Schwartz
Proceedings of the National Academy of Sciences, 1995•National Acad SciencesThe 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 …
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 …
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.
National Acad Sciences