THE LOW-DENSITY-LIPOPROTEIN RECEPTOR-RELATED PROTEIN, A MULTIFUNCTIONAL APOLIPOPROTEIN-E RECEPTOR, MODULATES HIPPOCAMPAL NEURITE DEVELOPMENT

The epsilon 4 allele of apolipoprotein E (apoE) is an important risk f actor for Alzheimer's disease. A major neuronal receptor for apoE with in the brain is the low-density lipoprotein receptor-related protein ( LRP). Using primary cultured hippocampal neurons, we examined the role of LRP in early neuronal development. LRP, as well as a 39-kDa protei n that regulates its activity, is localized abundantly in developing n eurons. Both the 39-kDa protein and an anti-LRP antibody inhibited neu rite outgrowth of primary hippocampal neurons cultured in either serum -containing medium or on cortical astrocyte monolayers in serum-free m edium, It is noteworthy that microtubule-associated protein-2 immunore active process outgrowth was decreased significantly in hippocampal ne urons cultured on cortical astrocytes derived from apoE-deficient mice and was not diminished further following incubation with LRP inhibito rs. Thus, these results suggest that LRP can influence aspects of neur onal process development and that apoE-containing lipoproteins may be one of the major LRP ligands that can contribute to this process.