EXPRESSION OF THE LOW-AFFINITY NERVE GROWTH-FACTOR RECEPTOR ENHANCES BETA-AMYLOID PEPTIDE TOXICITY

The low-affinity nerve growth factor receptor (NGFR) p75(NGFR) induces apoptosis in the absence of nerve growth factor (NGF) binding but enh ances neural survival when bound by NGF. Basal forebrain cholinergic n eurons express the highest levels of p75(NGFR) in the adult human brai n and are preferentially involved in Alzheimer disease, raising the qu estion of whether there may be a functional relationship between the e xpression of p75(NGFR) and basal forebrain cholinergic neuronal degene ration in Alzheimer disease. The expression of p75(NGFR) by wild-type and mutant PC12 cells potentiated cell death induced by beta-amyloid p eptide. NGF binding to p75(NGFR) inhibited the toxicity of beta-amyloi d peptide, whereas NGF binding to TrkA, the high-affinity NGFR, enhanc ed it. These results suggest a possible link between beta-amyloid pept ide toxicity and preferential degeneration of cells expressing p75(NGF R).