p75NTR-ECD, a soluble and diffusible molecule, is physiologically shed by TACE,16 and its shedding is considered to be a critical switch event that determines the balance between the enhancement effect on Aβ production and neurotoxicity of full-length p75NTR and the potential beneficial effect on blocking the toxicity of the Aβ oligomer of the p75NTR-ECD.9, 10 Thus, p75NTR-ECD may be an important modulating molecule in AD pathogenesis. The gene discussed is ECD; the disease is Alzheimer disease.