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 enhances neural survival when bound by NGF. Basal forebrain cholinergic neurons express the highest levels of p75(NGFR) in the adult human brain and are preferentially involved in Alzheimer disease, raising the question of whether there may be a functional relationship between the expression of p75(NGFR) and basal forebrain cholinergic neuronal degeneration in Alzheimer disease. The expression of p75(NGFR) by wild-type and mutant PC12 cells potentiated cell death induced by beta-amyloid peptide. NGF binding to p75(NGFR) inhibited the toxicity of beta-amyloid peptide, whereas NGF binding to TrkA, the high-affinity NGFR, enhanced it. These results suggest a possible link between beta-amyloid peptide toxicity and preferential degeneration of cells expressing p75(NGFR).