Amyloid (APP) Precursor 770 Fragments
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Introduction
APP is a 110-130 kDa transmembrane cell surface glycoprotein containing N and O, linked sugars. The largest region of the molecule is the extracellular domain. This domain contains a cysteine-rich region of approximately 200 amino acids, located at the N-terminus of the protein. It has a single transmembrane domain towards the carboxy terminus and a short cytoplasmic tail. APP contains a domain very similar to the Kunitz family of serine protease inhibitors, and the APP protein is homologous to the protease protease nexin-II2.
Mechanism of action
Vascular endothelial cells express amyloid beta precursor protein (APP) 770, a different APP isoform from neuronal APP695, and produce Aβ. Since the soluble APP cleavage product sAPP is considered a possible marker for the diagnosis of Alzheimer's Disease (AD), sAPP has been widely measured as a mixture of these variants. Researcher hypothesized that the measurement of endothelial APP770 cleavage products in patients with neuronal APP695 can distinguish between endothelial cells and neurological dysfunction. Using their newly developed sAPP770 ELISA system, they observed that inflammatory cytokines significantly enhance endothelial cell secretion of sAPP770. In addition, some scientists discovered that sAPP770 is rapidly released from activated platelets. They also found that cerebrospinal fluid mainly contains sAPP695, while serum mainly contains sAPP770. Finally, to test their hypothesis that sAPP770 may be an indicator of endothelial dysfunction, they applied APP770 ELISA to patients with acute coronary syndrome (ACS), in which endothelial damage and platelet activation lead to fibrous plaque destruction and thrombosis. The development of biomarkers is critical to promoting ACS diagnosis in clinical practice. The results showed a significant increase in plasma sAPP770 levels in patients with ACS.
Application of Amyloid (APP) Precursor 770 Fragments
APP plays a major role in regulating several important cellular functions, particularly in the nervous system, which involves synaptogenesis and synaptic plasticity. The secretory extracellular domain of APP, sAPPa, acts as a growth factor for many types of cells and promotes neuronal neurogenesis after mitosis. Since the soluble APP cleavage product sAPP is considered a possible marker for the diagnosis of AD, sAPP has been widely measured as a mixture of these variants. In myocardial infarction model rats, the increase in plasma sAPP precedes the release of myocardial enzymes, and markers for acute myocardial infarction are currently used. These findings raise the possibility that sAPP770 may become a useful biomarker for ACS.
References
- Haass, C., Koo, E. H., Mellon, A., Hung, A. Y., & Selkoe, D. J. (1992). Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments. Nature, 357(6378), 500.
- Ashall, F., & Goate, A. M. (1994). Role of the β-amyloid precursor protein in Alzheimer's disease. Trends in biochemical sciences, 19(1), 42-46.
- Jefferson, T., Causevic, M., Auf dem Keller, U., Schilling, O., Isbert, S., Geyer, R., ... & Bond, J. S. (2011). The metalloprotease meprin β generates nontoxic N-terminal amyloid precursor protein fragments in vivo. Journal of Biological Chemistry, jbc-M111.
