Translational Control of BACE1 May Go Awry in Alzheimer's Disease

Our understanding of the mechanisms whereby BACE1, the aspartyl protease required for the initial cleavage of APP to generate amyloid-beta (A beta), is regulated in Alzheimer's disease (AD) remains incomplete. In this issue of Neuron, O'Connor and coworkers show how energy deprivation, a potential risk factor in AD, triggers the phosphorylation of the translation initiation factor eIF2 alpha to elevate the translation efficiency of a set of stress-related transcripts, including that of BACE1, and increases the level of BACE1, thereby accelerating amyloidogenesis.