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Open Access Highly Accessed Review

APP processing in Alzheimer's disease

Yun-wu Zhang1*, Robert Thompson2, Han Zhang12 and Huaxi Xu12*

Author Affiliations

1 Institute for Biomedical Research, Xiamen University, 422 SiMingNanLu, Xiamen 361005, Fujian, PR China

2 Neurodegenerative Disease Research Program, Sanford-Burnham Institute for Medical Research, 10901 North Torrey Pines Road, La Jolla 92037, CA, USA

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Molecular Brain 2011, 4:3  doi:10.1186/1756-6606-4-3

Published: 7 January 2011


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