Proteolytic cleavage of the Alzheimer's disease amyloid A4 precursor protein

Amyloid A4 protein (beta-protein) is deposited in the brain of a patient with Alzheimer's disease (AD) as one of the main components of extracellular cerebrovascular amyloid, as well as neurofibrillary tangles. It is derived from a precursor protein, and its formation has been considered to be a rate-limiting step for brain degeneration in AD. In this article, proteolytic cleavage events that can degrade amyloid precursor protein are reviewed with respect to how the topographical distribution of the proteinase and its substrates disturbs normal processing steps in AD brain.