APP (C99 Fragment) Monoclonal Antibody (Clone 8G4)

Amyloid precursor protein (APP) is a type I transmembrane protein that has a central role in the pathogenesis of Alzheimer’s disease, as well as additional roles in brain development, neuronal plasticity, and memory.¹ APP is cleaved by β-secretase (BACE) in neuronal endosomes during amyloidogenic processing of APP, generating the C-terminal C99 fragment, which is localized to the endoplasmic membrane.^2,3 C99 is further cleaved by γ-secretase, liberating the APP intracellular domain (AICD) and generating amyloid-β (Aβ) peptides of various lengths, including Aβ40 (Item No. 21617) and Aβ42 (Item No. 20574), which are hallmarks of Alzheimer's disease. APP can also be cleaved by α-secretase during non-amyloidogenic processing of APP, which occurs at the neuronal plasma membrane and generates the neuroprotective soluble APP fragment sAPPα, as well as a variety of other fragments, including the C47 fragment.^1,4 Transgenic mice expressing mutant forms of APP exhibit extracellular Aβ deposits in the brain, as well as cognitive dysfunction, and are widely used models of Alzheimer’s disease.⁵ Intraneuronal C99 levels are increased in the transgenic APP^E693Q mouse model of Alzheimer’s disease, as well as postmortem frontal cortex from patients with sporadic Alzheimer's disease.^3,6 Cayman's APP (C99 Fragment) Monoclonal Antibody (Clone 8G4) can be used for ELISA and immunohistochemistry (IHC) applications. The antibody recognizes the C-terminal region corresponding to the C99 fragment to detect intact APP, as well as the C47 APP fragment.

WARNING This product is not for human or veterinary use.

1. Müller, U.C., Deller, T., and Korte, M. Not just amyloid: Physiological functions of the amyloid precursor protein family. Nat. Rev. Neurosci. 18(5), 281-298 (2017).

2. Zhao, J., Liu, X., Xia, W., et al. Targeting amyloidogenic processing of APP in Alzheimer’s disease. Front. Mol. Neurosci. 13, 137 (2020).

3. Lauritzen, I., Pardossi-Piquard, R., Bourgeois, A., et al. Does intraneuronal accumulation of carboxyl-terminal fragments of the amyloid precursor protein trigger early neurotoxicity in Alzheimer’s disease? Curr. Alzheimer Res. 16(5), 453-457 (2019).

4. Schrader-Fischer, G., Staufenbiel, M., and Paganetti, P.A. Insertion of lysosomal targeting sequences to the amyloid precursor protein reduces secretion of βA₄. J. Neurochem. 68(4), 1571-1580 (1997).

5. Sasaguri, H., Nilsson, P., Hashimoto, S., et al. APP mouse models for Alzheimer’s disease preclinical studies. EMBO J. 36(17), 2473-2487 (2017).

6. Pulina, M.V., Hopkins, M., Haroutunian, V., et al. C₉₉ selectively accumulates in vulnerable neurons in Alzheimer’s disease. Alzheimers Dement. 16(2), 273-282 (2020).