Abstract
The 99-amino-acid-long APP-carboxy-terminal fragment, named C99, is a membrane-bound peptide generated from the amyloid precursor protein (APP) by β-secretase cleavage and is the direct precursor of amyloid beta (Aβ). Here we describe a method for the quantification of C99. The amount of C99 is an indicative value of the amyloid pathology in an Alzheimer’s disease (AD) model, and could be used as a marker to study AD progression in comprehensive experiments, including screening for new compounds and repurposing of drugs to treat AD.
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References
Glenner GG, Wong CW (1984) Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 120:885–890
Masters CL, Multhaup G, Simms G et al (1985) Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer’s disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J 4:2757–2763
Grundke-Iqbal I, Iqbal K, Tung YC et al (1986) Abnormal phosphorylation of the microtubule-associated protein tau (tau) in Alzheimer cytoskeletal pathology. Proc Natl Acad Sci U S A 83:4913–4917
Haass C, Selkoe DJ (1993) Cellular processing of beta-amyloid precursor protein and the genesis of amyloid beta-peptide. Cell 75:1039–1042
Gandy S (2005) The role of cerebral amyloid beta accumulation in common forms of Alzheimer disease. J Clin Invest 115:1121–1129
Jarrett JT, Berger EP, Lansbury PT Jr (1993) The carboxy terminus of the beta amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer’s disease. Biochemistry 32:4693–4697
Hsiao K, Chapman P, Nilsen S et al (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274:99–102
Nunan J, Shearman MS, Checler F et al (2001) The C-terminal fragment of the Alzheimer’s disease amyloid protein precursor is degraded by a proteasome-dependent mechanism distinct from gamma-secretase. Eur J Biochem 268:5329–5336
Lashuel HA, Hartley D, Petre BM et al (2002) Neurodegenerative disease: amyloid pores from pathogenic mutations. Nature 418:291
Jin LW, Hua DH, Shie FS et al (2002) Novel tricyclic pyrone compounds prevent intracellular APP C99-induced cell death. J Mol Neurosci 19:57–61
Lauritzen I, Pardossi-Piquard R, Bauer C et al (2012) The beta-secretase-derived C-terminal fragment of betaAPP, C99, but not Abeta, is a key contributor to early intraneuronal lesions in triple-transgenic mouse hippocampus. J Neurosci 32:16243–16255a
Criterion XT Precast Gel Instruction Guide (Bio-Rad, catalog #345-9898). http://www.bio-rad.com/webroot/web/pdf/lsr/literature/MS4110130B.pdf
Acknowledgements
This study was supported by the foundation for applied medical research-Fundación para la Investigación Médica Aplicada (FIMA, Spain) and the fund for health research-Fondo de Investigación Sanitaria (FIS project 11/02861).
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García-Osta, A., Cuadrado-Tejedor, M. (2016). Advanced Assay Monitoring APP-Carboxyl-Terminal Fragments as Markers of APP Processing in Alzheimer Disease Mouse Models. In: Castrillo, J., Oliver, S. (eds) Systems Biology of Alzheimer's Disease. Methods in Molecular Biology, vol 1303. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2627-5_5
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DOI: https://doi.org/10.1007/978-1-4939-2627-5_5
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