p75 NTR , a nerve growth factor co-receptor that has been implicated in apoptosis of neurons, is structurally related to Fas and the receptors for tumor necrosis factor-␣ that display ligand independent assembly into trimers. Using embryonic day 17 fetal rat cortical neurons and p75 NTR -expressing NIH-3T3 cells, we now show that p75 NTR exists as a trimer as well as a monomer. Furthermore, we have reported and others have confirmed that amyloid ␤ binds p75 NTR , and that this binding leads to

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... poptotic cell death. We now report that amyloid ␤ binds to trimers of p75 NTR as well as to p75 NTR monomers but not to the p140 trkA , the nerve growth factor co-receptor that mediates neuronal survival. Furthermore, amyloid ␤ activates p75 NTR , strongly inducing the transcription of c-Jun mRNA and stimulating the stress-activated c-Jun NH 2 -terminal kinase, as measured by phosphorylation of its substrate (glutathione S-transferase-c-Jun-(1-79)). Our data suggest that p75 NTR may be present as a preformed trimer that binds amyloid ␤ to induce receptor activation, and support the hypothesis that p75 NTR activation by amyloid ␤ is causally related to Alzheimer's disease.