Amyloid beta-protein precursor: new clues to the genesis of Alzheimer's disease.

Research into the cellular processing and functional properties of the amyloid beta-protein precursor (beta PP) and its secreted derivatives is rapidly accelerating and drawing interest from many investigators outside the field of Alzheimer's disease pathobiology. Recent in vitro studies suggest multiple activities for the major secreted product, beta PPs, including protease inhibition, growth promotion, neuroprotection and stimulation of a signal transduction pathway. Surprisingly, the hydrophobic amyloid beta-protein fragment is also constitutively secreted. Its generation occurs in part during the endocytosis of cell-surface beta PP molecules. Processing of beta PP via amyloidogenic versus non-amyloidogenic pathways is under complex regulation by various first and second messengers. Analyses of beta PP missense mutations and of the effects of apolipoprotein E genotype lend new support to the hypothesis that accelerated amyloid beta protein deposition plays a pivotal role in the genesis of Alzheimer's disease.