APP processing in Alzheimer's disease

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 beta-amyloid (A beta). Multiple lines of evidence demonstrate that overproduction/aggregation of A beta in the brain is a primary cause of AD and inhibition of A beta generation has become a hot topic in AD research. A beta is generated from beta-amyloid precursor protein (APP) through sequential cleavages first by beta-secretase and then by gamma-secretase complex. Alternatively, APP can be cleaved by alpha-secretase within the A beta domain to release soluble APP alpha and preclude A beta 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.