EFFECTS OF THE AMYLOID PROTEIN-PRECURSOR OF ALZHEIMERS-DISEASE AND OTHER LIGANDS OF THE LDL RECEPTOR-RELATED PROTEIN ON NEURITE OUTGROWTH FROM SYMPATHETIC NEURONS IN CULTURE

The amyloid protein precursor (APP) of Alzheimer's disease can stimula te neurite outgrowth in vitro. The receptor responsible for this effec t has not been identified. Kunitz protease inhibitor (KPI)-containing forms of APP bind to the lon-density lipoprotein receptor-related prot ein (LRP), As LRP may regulate neurite outgrowth, we examined whether the effects of are mediated by LRP. Inhibitors of LRP decreased neurit e outgrowth from chick sympathetic neurons. Most LRP ligands (alpha 2- macroglobulin, lactoferrin, and lipoprotein lipase) stimulated outgrow th, However, in soluble form, the KPI-containing APP(751) was a weak i nhibitor of outgrowth. In substrate-bound form, both APP(751) and APP( 695) (which does not bind to LRP) stimulated outgrowth. Thus the effec t of substrate-bound APP on neurite outgrowth is not mediated by LRP, (C) 1998 Federation of European Biochemical Societies.