Amyloid-beta precursor protein (APP) is the source of the amyloid-beta (Ab) peptide found in neuritic plaques of Alzheimer's disease (AD) patients. APP is aglycosylated transmembrane protein with a long extracellular N-terminal domain, a short intracellular C-terminal domain, and an Abeta-segment of intermediate length shared between the intra- and extracellular regions. APP is cleaved by alpha-secretase immediately before or after reaching the cell surface, releasing the nonamyloidogenic secreted form of the N-terminal soluble APP fragment (sAPPa). APP molecules that are not cleaved by alpha-secretase are internalized, and subjected to beta-site cleavage by beta-secretase, leaving behind a membrane-bound C-terminal stub. This terminal stub is the substrate for gamma-secretase, which cleaves the molecule at gamma-site(s) to release the 40aa, 42aa, or 43aa-long Ab peptides. Processing of APP by beta and gamma-secretases occurs under normal physiological conditions, indicating that all fragments of APP, including Ab, play roles in normal physiology. In neurons, around 95% of APP is cleaved by gamma-secretases while 5% is cleaved by beta-secretase. Excessive generation of Ab and its subsequent oligomerization and fibrillation leads to the detrimental effects of AD. Reductions in the level or activity of certain APP fragments, in addition to accumulation of Ab, may play a critical role in the cognitive dysfunction associated aith AD, especially in the early stages of the disease. APP fragments including Ab regulate key neural functions including cell excitability, synaptic transmission, long-term potentiation, behavorial learning, and memory.
Applications:
Suitable for use in Western Blot, Immunoprecipitation, Immunofluorescence, ELISA and Immunohistochemistry. Other applications not tested.
Recommended Dilution:
Immunohistochemistry (Formalin fixed paraffin embedded): 5ug/ml
Optimal dilutions to be determined by the researcher.
Storage and Stability:
May be stored at 4 degrees C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Aliquots are stable for at least 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.