Aβ is increased in AD and has been shown to bind p75NTR to induce neuronal death.13, 14 NTs, which also bind p75NTR and protect neurons from Aβ-induced neurotoxicity in vitro,22 are decreased in AD.23 Additionally, increased p75NTR and decreased TrkA expression have been reported in AD.15, 16, 24, 25 Our data combined with the published studies demonstrate that DR6, p75NTR, and Aβ are all upregulated in AD brains, whereas NTs and TrkA are downregulated, suggesting a potential role for the DR6/p75NTR receptor complex in neuronal cell death in AD. This evidence concerns the gene TNFRSF21 and Alzheimer disease.