APP processing in Alzheimer's disease

Abstract

An important pathological feature of Alzheimer's disease (AD) is the presence of extracellular senile plaques in the brain. Senile plaques are composed of aggregations of small peptides called -amyloid (A). Multiple lines of evidence demonstrate that overproduction/aggregation of A in the brain is a primary cause of AD and inhibition of A generation has become a hot topic in AD research. A is generated from -amyloid precursor protein (APP) through sequential cleavages first by -secretase and then by -secretase complex. Alternatively, APP can be cleaved by -secretase within the A domain to release soluble APP and preclude A generation. Cleavage of APP by caspases may also contribute to AD pathologies. Therefore, understanding the metabolism/processing of APP is crucial for AD therapeutics. Here we review current knowledge of APP processing regulation as well as the patho/physiological functions of APP and its metabolites. © 2011 Zhang et al; licensee BioMed Central Ltd.