Encyclopedia of Signaling Molecules

2018 Edition
| Editors: Sangdun Choi


  • Katherine A. SouthamEmail author
  • Fiona A. Stennard
  • David H. Small
Reference work entry
DOI: https://doi.org/10.1007/978-3-319-67199-4_101532


Historical Background

Amyloid precursor protein (APP) is a cell-surface protein that has been well studied for its role in Alzheimer’s disease (AD), a progressive neurodegenerative disorder that is the most common form of dementia in the elderly. In 1906, Alois Alzheimer described a case of presenile dementia in which amyloid plaques were present in the brain. Later, the primary component of these plaques was identified as a small protein containing 36–43 amino acid residues (Glenner and Wong 1984; Masters et al. 1985), which has since been named the β-amyloid protein (Aβ). Aβ is produced by proteolytic cleavage of APP (Kang et al. 1987). Mutations in APP that enhance the production of specific Aβ species have been shown to accelerate AD progression (Van Cauwenberghe et al. 2016). In addition, triploidy of chromosome 21 (Down...

This is a preview of subscription content, log in to check access.


  1. Aydin D, Weyer SW, Muller UC. Functions of the APP gene family in the nervous system: insights from mouse models. Exp Brain Res. 2012;217:423–34.PubMedCrossRefGoogle Scholar
  2. Barrett PJ, Song Y, Van Horn WD, Hustedt EJ, Schafer JM, Hadziselimovic A, et al. The amyloid precursor protein has a flexible transmembrane domain and binds cholesterol. Science. 2012;336:1168–71.PubMedPubMedCentralCrossRefGoogle Scholar
  3. Baumkotter F, Schmidt N, Vargas C, Schilling S, Weber R, Wagner K, et al. Amyloid precursor protein dimerization and synaptogenic function depend on copper binding to the growth factor-like domain. J Neurosci. 2014;34:11159–72.PubMedCrossRefGoogle Scholar
  4. Clarris HJ, Key B, Beyreuther K, Masters CL, Small DH. Expression of the amyloid protein precursor of Alzheimer’s disease in the developing rat olfactory system. Brain Res Dev Brain Res. 1995;88:87–95.PubMedCrossRefGoogle Scholar
  5. Coulson EJ, Paliga K, Beyreuther K, Masters CL. What the evolution of the amyloid protein precursor supergene family tells us about its function. Neurochem Int. 2000;36:175–84.PubMedCrossRefGoogle Scholar
  6. Dahms SO, Hoefgen S, Roeser D, Schlott B, Guhrs KH, Than ME. Structure and biochemical analysis of the heparin-induced E1 dimer of the amyloid precursor protein. Proc Natl Acad Sci USA. 2010;107:5381–6.PubMedPubMedCentralCrossRefGoogle Scholar
  7. Dawkins E, Small DH. Insights into the physiological function of the beta-amyloid precursor protein: beyond Alzheimer’s disease. J Neurochem. 2014;129:756–69.PubMedPubMedCentralCrossRefGoogle Scholar
  8. Deyts C, Thinakaran G, Parent AT. APP Receptor? To Be or Not To Be. Trends Pharmacol Sci. 2016;37:390–411.PubMedPubMedCentralCrossRefGoogle Scholar
  9. Glenner GG, Wong CW. Alzheimer’s disease and Down’s syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem Biophys Res Commun. 1984;122:1131–5.PubMedCrossRefGoogle Scholar
  10. Ho A, Sudhof TC. Binding of F-spondin to amyloid-beta precursor protein: a candidate amyloid-beta precursor protein ligand that modulates amyloid-beta precursor protein cleavage. Proc Natl Acad Sci USA. 2004;101:2548–53.PubMedPubMedCentralCrossRefGoogle Scholar
  11. Hoefgen S, Coburger I, Roeser D, Schaub Y, Dahms SO, Than ME. Heparin induced dimerization of APP is primarily mediated by E1 and regulated by its acidic domain. J Struct Biol. 2014;187:30–7.PubMedCrossRefGoogle Scholar
  12. Jonsson T, Atwal JK, Steinberg S, Snaedal J, Jonsson PV, Bjornsson S, et al. A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Nature. 2012;488:96–9.PubMedCrossRefGoogle Scholar
  13. Kang J, Lemaire HG, Unterbeck A, Salbaum JM, Masters CL, Grzeschik KH, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature. 1987;325:733–6.PubMedCrossRefGoogle Scholar
  14. Liu X, Yu X, Zack DJ, Zhu H, Qian J. TiGER: a database for tissue-specific gene expression and regulation. BMC Bioinformatics. 2008;9:271.PubMedPubMedCentralCrossRefGoogle Scholar
  15. Lourenco FC, Galvan V, Fombonne J, Corset V, Llambi F, Muller U, et al. Netrin-1 interacts with amyloid precursor protein and regulates amyloid-beta production. Cell Death Differ. 2009;16:655–63.PubMedPubMedCentralCrossRefGoogle Scholar
  16. Masters CL, Simms G, Weinman NA, Multhaup G, McDonald BL, Beyreuther K. Amyloid plaque core protein in Alzheimer disease and Down syndrome. Proc Natl Acad Sci U S A. 1985;82:4245–9.PubMedPubMedCentralCrossRefGoogle Scholar
  17. McLoughlin DM, Miller CC. The FE65 proteins and Alzheimer’s disease. J Neurosci Res. 2008;86:744–54.PubMedCrossRefGoogle Scholar
  18. Müller UC, Zheng H. Physiological functions of APP family proteins. Cold Spring Harb Perspect Med. 2012;2:a006288.PubMedPubMedCentralCrossRefGoogle Scholar
  19. Priller C, Bauer T, Mitteregger G, Krebs B, Kretzschmar HA, Herms J. Synapse formation and function is modulated by the amyloid precursor protein. J Neurosci. 2006;26:7212–21.PubMedCrossRefGoogle Scholar
  20. Rice HC, Townsend M, Bai J, Suth S, Cavanaugh W, Selkoe DJ, et al. Pancortins interact with amyloid precursor protein and modulate cortical cell migration. Development. 2012;139:3986–96.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Rossjohn J, Cappai R, Feil SC, Henry A, McKinstry WJ, Galatis D, et al. Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol. 1999;6:327–31.PubMedCrossRefGoogle Scholar
  22. Van Cauwenberghe C, Van Broeckhoven C, Sleegers K. The genetic landscape of Alzheimer’s disease: clinical implications and perspectives. Genet Med. 2016;18:421–30.PubMedCrossRefGoogle Scholar
  23. Wang Z, Wang B, Yang L, Guo Q, Aithmitti N, Songyang Z, et al. Presynaptic and postsynaptic interaction of the amyloid precursor protein promotes peripheral and central synaptogenesis. J Neurosci. 2009;29:10788–801.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Katherine A. Southam
    • 1
    Email author
  • Fiona A. Stennard
    • 1
  • David H. Small
    • 1
  1. 1.Menzies Institute for Medical ResearchUniversity of TasmaniaHobartAustralia