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Review
. 2011 Jan 7:4:3.
doi: 10.1186/1756-6606-4-3.

APP processing in Alzheimer's disease

Yun-wu Zhang  1 , Robert Thompson, Han Zhang, Huaxi Xu
Affiliations
Review

APP processing in Alzheimer's disease

Yun-wu Zhang et al. Mol Brain. .

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 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.

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Figures

Figure 1
Figure 1
Schematic diagram of APP processing (not drawn in proportion). It is not clear whether caspases cleave membrane-associated APP forms or released AICD.
See this image and copyright information in PMC

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