New Alzheimer’s target

Much of the work on potential anti-Alzheimer’s disease drugs has been focused on compounds that reduce the accumulation of neurotoxic amyloid-β peptide in the brain. This has met with little success, in part because agents that block γ-secretase cause severe side effects because they also block processing of Notch, a signalling protein essential for many homeostatic functions. Now the discovery of a γ-secretase activating protein (GSAP) that selectively controls amyloid-β generation without influencing Notch cleavage suggests a possible new target for anti-Alzheimer’s drugs. The anticancer drug imatinib (Gleevec), known to inhibit amyloid-β formation without affecting Notch cleavage, is shown to act via an effect on GSAP. This suggests that GSAP inhibitors that can cross the blood–brain barrier (unlike imatinib) may hold promise for treating Alzheimer’s disease. [Letter p. 95; News & Views p. 36]