Lowering of Amyloid-Beta by β-Secretase Inhibitors - Some Informative Failures

Some trials fail because the experimental treatment proves to be no different than a control or standard intervention. Others fail because of unacceptable side effects. In this issue of the Journal, an article by Egan et al.(1) and a letter to the editor by Henley et al.(2) describe a third reason for failure - a treatment worsens the target symptoms. The therapeutic intervention of lowering brain amyloid-beta (A beta) peptide levels to treat patients with Alzheimer's disease is based on a conceptual model in which accumulation of A beta is causally related to cognitive decline. The model is rooted in the inseparability . . .