The beta-amyloid precursor protein (APP) and Alzheimer's disease: does the tail wag the dog?

The beta-amyloid precursor protein has been the focus of much attention from the Alzheimer's disease community for the past decade and a half. The beta-amyloid precursor protein holds a pivotal position in Alzheimer's disease research because it is the precursor to the amyloid beta-protein which many believe plays a central role in Alzheimer's disease pathogenesis. It was also the first gene in which mutations associated with inherited Alzheimer's disease were found. Although the molecular details of the generation of amyloid beta-protein from beta-amyloid precursor protein are being unraveled, the actual physiological functions of beta-amyloid precursor protein are far from clear. This situation is changing as accumulating new evidence suggests that the C-terminal cytosolic tail of beta-amyloid precursor protein may have multiple biological activities, ranging from axonal transport to nuclear signaling. This article reviews the current state of knowledge about the biological functions of beta-amyloid precursor protein.