LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN MEDIATES APOLIPOPROTEIN E-DEPENDENT NEURITE OUTGROWTH IN A CENTRAL NERVOUS SYSTEM-DERIVED NEURONAL CELL-LINE

The epsilon 4 allele of apolipoprotein E (apoE) is a major risk factor for Alzheimer disease, suggesting that apoE may directly influence ne urons in the aging brain. Recent data suggest that apoE-containing lip oproteins can influence neurite outgrowth in an isoform-specific fashi on. 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 protei n that regulates ligand binding to the low density lipoprotein recepto r-related protein (LRP). Anti-LRP antibody also completely abolished t he neurite-promoting effect of apoE3. Understanding isoform-specific c ell biological processes mediated by apoE-LRP interactions in central nervous system neurons may provide insight into Alzheimer disease path ogenesis.