Skip to main content
SpringerLink
Log in

The Function of the Amyloid Precursor Protein Family

  • Chapter
Book cover Abeta Peptide and Alzheimer’s Disease

Abstract

The purification and sequencing of the β-amyloid peptide (Aβ) [1]–[3] led to the cloning of the Alzheimer’s disease (AD) amyloid precursor protein (APP) gene in the late 1980s [4]. Despite an extensive research effort toward understanding the function of APP, its physiological role remains poorly defined. This review will summarize the key activities associated with APP and its paralogues the amyloid precursor like proteins 1 and 2 (APLP1 and APLP2, respectively).

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Glenner GG, Wong CW. Alzheimer’s disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem Biophys Res Commun 1984;120:885–90.

    PubMed  CAS  Google Scholar 

  2. Masters CL, Multhaup G, Simms G, et al. 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 1985;4:2757–63.

    PubMed  CAS  Google Scholar 

  3. Masters CL, Simms G, Weinman NA, et al. Amyloid plaque core protein in Alzheimer’s disease and Down syndrome. Proc Natl Acad Sci U S A 1985;82:4245–9.

    PubMed  CAS  Google Scholar 

  4. Kang J, Lemaire H, Unterbeck A, et al. The precursor of Alzheimer’s disease amyloid A4 protein resembles a cell-surface receptor. Nature 1987; 325:733–6.

    PubMed  CAS  Google Scholar 

  5. Goldgaber D, Lerman MI, McBride OW, et al. Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer’s disease. Science 1987;235:877–80.

    PubMed  CAS  Google Scholar 

  6. Tanzi RE, Gusella JF, Watkins PC, et al. Amyloid β protein gene: cDNA, mRNA distribution and genetic linkage near the Alzheimer locus. Science 1987; 235:880–4.

    PubMed  CAS  Google Scholar 

  7. Yoshikai S, Sasaki H, Doh-ura K, et al. Genomic organization of the human-amyloid beta-protein precursor gene. Gene 1991;102:291–2.

    PubMed  CAS  Google Scholar 

  8. Panegyres PK. The functions of the amyloid precursor protein gene. Rev Neurosci 2001;12:1–39.

    PubMed  CAS  Google Scholar 

  9. Beyreuther K, Pollwein P, Multhaup G, et al. Regulation and expression of the Alzheimer’s beta/A4 amyloid protein precursor in health, disease, and Down’s syndrome. Ann N Y Acad Sci 1993;695:91–102.

    PubMed  CAS  Google Scholar 

  10. Sandbrink R, Masters CL, Beyreuther K. βA4-amyloid protein precursor mRNA isoforms without exon 15 are ubiquitously expressed in rat tissues including brain, but not in neurons. J Biol Chem 1994;269:1510–7.

    PubMed  CAS  Google Scholar 

  11. Shioi J, Pangalos MN, Ripellino JA, et al. The Alzheimer amyloid precursor proteoglycan (appican) is present in brain and is produced by astrocytes but not by neurons in primary neural cultures. J Biol Chem 1995;270:11839–44.

    PubMed  CAS  Google Scholar 

  12. Rossjohn J, Cappai R, Feil SC, et al. Crystal structure of the N-terminal, growth factor-like domain of Alzheimer amyloid precursor protein. Nat Struct Biol 1999;6:327–31.

    PubMed  CAS  Google Scholar 

  13. Dulubova I, Ho A, Huryeva I, et al. Threedimensional structure of an independently folded extracellular domain of human amyloid-beta precursor protein. Biochemistry 2004;43:9583–8.

    PubMed  CAS  Google Scholar 

  14. Barnham KJ, McKinstry WJ, Multhaup G, et al. Structure of the Alzheimer’s disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis. J Biol Chem 2003; 278:17401–7.

    PubMed  CAS  Google Scholar 

  15. Wang Y, Ha Y. The x-ray structure of an antiparallel dimer of the human amyloid precursor protein E2 domain. Mol Cell 2004;15:343–53.

    PubMed  CAS  Google Scholar 

  16. Small DH, Nurcombe V, Reed G, et al. A heparinbinding domain in the amyloid protein precursor of Alzheimer’s disease is involved in the regulation of neurite outgrowth. J Neurosci 1994;14:2117–27.

    PubMed  CAS  Google Scholar 

  17. Hesse L, Beher D, Masters CL, Multhaup G. The beta A4 amyloid precursor protein binding to copper. FEBS Lett 1994;349:109–16.

    PubMed  CAS  Google Scholar 

  18. Multhaup G, Schlicksupp A, Hesse L, et al. The amyloid precursor protein of Alzheimer’s disease in the reduction of copper(II) to copper(I). Science 1996;271:1406–9.

    PubMed  CAS  Google Scholar 

  19. Bush AI, Multhaup G, Moir RD, et al. A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer’s disease. J Biol Chem 1993;268:16109–12.

    PubMed  CAS  Google Scholar 

  20. White AR, Reyes R, Mercer JF, et al. Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice. Brain Res 1999;842:439–44.

    PubMed  CAS  Google Scholar 

  21. Maynard CJ, Cappai R, Volitakis I, et al. Overexpression of Alzheimer’s disease amyloid-beta opposes the age-dependent elevations of brain copper and iron. J Biol Chem 2002;277:44670–6.

    PubMed  CAS  Google Scholar 

  22. Bayer TA, Schafer S, Simons A, et al. Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Abeta production in APP23 transgenic mice. Proc Natl Acad Sci U S A 2003;100: 14187–92.

    PubMed  CAS  Google Scholar 

  23. Phinney AL, Drisaldi B, Schmidt SD, et al. In vivo reduction of amyloid-beta by a mutant copper transporter. Proc Natl Acad Sci U S A 2003;100:14193–8.

    PubMed  CAS  Google Scholar 

  24. White AR, Multhaup G, Maher F, et al. The Alzheimer’s disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures. J Neurosci 1999;19:9170–9.

    PubMed  CAS  Google Scholar 

  25. White AR, Multhaup G, Galatis D, et al. Contrasting, species-dependent modulation of copper-mediated neurotoxicity by the Alzheimer’s disease amyloid precursor protein. J Neurosci 2002;22:365–76.

    PubMed  CAS  Google Scholar 

  26. Simons A, Ruppert T, Schmidt C, et al. Evidence for a copper-binding superfamily of the amyloid precursor protein. Biochemistry 2002;41:9310–20.

    PubMed  CAS  Google Scholar 

  27. Borchardt T, Camakaris J, Cappai R, et al. Copper inhibits beta-amyloid production and stimulates the non-amyloidogenic pathway of amyloid-precursorprotein secretion. Biochem J 1999;344 Pt 2:461–7.

    PubMed  CAS  Google Scholar 

  28. Borchardt T, Schmidt C, Camarkis J, et al. Differential effects of zinc on amyloid precursor protein (APP) processing in copper-resistant variants of cultured Chinese hamster ovary cells. Cell Mol Biol 2000;46:785–95.

    PubMed  CAS  Google Scholar 

  29. Donnelly RJ, Rasool CG, Bartus R, et al. Multiple forms of beta-amyloid peptide precursor RNAs in a single cell type. Neurobiol Aging 1988;9:333–8.

    PubMed  CAS  Google Scholar 

  30. Weidemann A, König G, Bunke D, et al. Identification, biogenesis, and localization of precursors of Alzheimer’s disease A4 amyloid protein. Cell 1989; 57:115–26.

    PubMed  CAS  Google Scholar 

  31. Kitaguchi N, Takahashi Y, Tokushima Y, et al. Novel precursor of Alzheimer’s disease amyloid protein shows protease inhibitory activity. Nature 1988;331:530–2.

    PubMed  CAS  Google Scholar 

  32. Oltersdorf T, Fritz LC, Schenk DB, et al. The secreted form of the Alzheimer’s amyloid precursor protein with the Kunitz domain is protease nexin-II. Nature 1989;341:144–7.

    PubMed  CAS  Google Scholar 

  33. Ponte P, Gonzalez-DeWhitt P, Schilling J, et al. A new A4 amyloid mRNA contains a domain homologous to serine proteinase inhibitors. Nature 1988;331:525–7.

    PubMed  CAS  Google Scholar 

  34. Tanzi RE, McClatchey AI, Lamperti ED, et al. Protease inhibitor domain encoded by an amyloid protein precursor mRNA associated with Alzheimer’s disease. Nature 1988;331:528–30.

    PubMed  CAS  Google Scholar 

  35. Dyrks T, Weidemann A, Multhaup G, et al. Identification, transmembrane orientation and biogenesis of the amyloid A4 precursor of Alzheimer’s disease. EMBO J 1988;7:949–57.

    PubMed  CAS  Google Scholar 

  36. Weidemann A, Eggert S, Reinhard FB, et al. A novel epsilon-cleavage within the transmembrane domain of the Alzheimer amyloid precursor protein demonstrates homology with Notch processing. Biochemistry 2002;41:2825–35.

    PubMed  CAS  Google Scholar 

  37. Cao X, Sudhof TC. Dissection of amyloid-beta precursor protein-dependent transcriptional transactivation. J Biol Chem 2004;279:24601–11.

    PubMed  CAS  Google Scholar 

  38. Cao X, Sudhof TC. A transcriptionally active complex of APP with Fe65 and histone acetyltransferase Tip60. Science 2001;293:115–20.

    PubMed  CAS  Google Scholar 

  39. von Rotz RC, Kohli BM, Bosset J, et al. The APP intracellular domain forms nuclear multiprotein complexes and regulates the transcription of its own precursor. J Cell Sci 2004;117:4435–48.

    Google Scholar 

  40. Selkoe DJ, Podlisny MB, Joachim CL, et al. Betaamyloid precursor protein of Alzheimer’s disease occurs as 110-to 135-kilodalton membrane-associated proteins in neural and nonneural tissues. Proc Natl Acad Sci U S A 1988;85:7341–5.

    PubMed  CAS  Google Scholar 

  41. Golde TE, Estus S, Usiak M, et al. Expression of beta amyloid protein precursor mRNAs: recognition of a novel alternatively spliced form and quantitation in Alzheimer’s disease using PCR. Neuron 1990; 4:253–67.

    PubMed  CAS  Google Scholar 

  42. Palmert MR, Podlisny MB, Witker DS, et al. The β-amyloid protein precursor of Alzheimer’s disease has soluble derivatives found in human brain and cerebrospinal fluid. Proc Natl Acad Sci U S A 1989; 86:6338–42.

    PubMed  CAS  Google Scholar 

  43. Olsson A, Csajbok L, Ost M, et al. Marked increase of beta-amyloid(1–42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury. J Neurol 2004;251:870–6.

    PubMed  CAS  Google Scholar 

  44. Xie Y, Yao Z, Chai H, et al. Potential roles of Alzheimer precursor protein A4 and beta-amyloid in survival and function of aged spinal motor neurons after axonal injury. J Neurosci Res 2003;73:557–64.

    PubMed  CAS  Google Scholar 

  45. Abe K, Tanzi RE, Kogure K. Selective induction of Kunitz-type protease inhibitor domain-containing amyloid precursor protein mRNA after persistent focal ischemia in rat cerebral cortex. Neurosci Lett 1991;125:172–4.

    PubMed  CAS  Google Scholar 

  46. Forloni G, Demicheli F, Giorgi S, et al. Expression of amyloid precursor protein mRNAs in endothelial, neuronal and glial cells: modulation by interleukin-1. Mol Brain Res 1992;16:128–34.

    PubMed  CAS  Google Scholar 

  47. Monning U, Konig G, Banati RB, et al. Alzheimer beta A4-amyloid protein precursor in immunocompetent cells. J Biol Chem 1992;267:23950–6.

    PubMed  CAS  Google Scholar 

  48. Li QX, Berndt MC, Bush AI, et al. Membraneassociated forms of the βA4 amyloid protein precursor of Alzheimer’s disease in human platelet and brain: surface expression on the activated human platelet. Blood 1994;84:133–42.

    PubMed  CAS  Google Scholar 

  49. Van Nostrand WE, Schmaier AH, Farrow JS, et al. Protease nexin-II (amyloid β-protein precursor): a platelet α-granule protein. Science 1990;248:745–8.

    PubMed  Google Scholar 

  50. Moir RD, Lynch T, Bush AI, et al. Relative increase in Alzheimer’s disease of soluble forms of cerebral a-β amyloid protein precursor containing the kunitz protease inhibitory domain. J Biol Chem 1998;273: 5013–9.

    PubMed  CAS  Google Scholar 

  51. Ho L, Fukuchi K, Younkin SG. The alternatively spliced Kunitz protease inhibitor domain alters amyloid beta protein precursor processing and amyloid beta protein production in cultured cells. J Biol Chem 1996;271:30929–34.

    PubMed  CAS  Google Scholar 

  52. Barrachina M, Dalfo E, Puig B, et al. Amyloid-beta deposition in the cerebral cortex in Dementia with Lewy bodies is accompanied by a relative increase in AbetaPP mRNA isoforms containing the Kunitz protease inhibitor. Neurochem Int 2005;46:253–60.

    PubMed  CAS  Google Scholar 

  53. Konig G, Monning U, Czech C, et al. Identification and differential expression of a novel alternative splice isoform of the beta A4 amyloid precursor protein (APP) mRNA in leukocytes and brain microglial cells. J Biol Chem 1992;267:10804–9.

    PubMed  CAS  Google Scholar 

  54. Pangalos MN, Efthimiopoulos S, Shioi J, et al. The chondroitin sulfate attachment site of appican is formed by splicing out exon 15 of the amyloid precursor gene. J Biol Chem 1995;270:10388–91.

    PubMed  CAS  Google Scholar 

  55. Morin PJ, Medina M, Semenov M, et al. Wnt-1 expression in PC12 cells induces exon 15 deletion and expression of L-APP. Neurobiol Dis 2004;16:59–67.

    PubMed  CAS  Google Scholar 

  56. De Strooper B, Annaert W. Where Notch and Wnt signaling meet. The presenilin hub. J Cell Biol 2001;152:F17–20.

    Google Scholar 

  57. 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.

    PubMed  CAS  Google Scholar 

  58. Daigle I, Li C. apl-1, a Caenorhabditis elegans gene encoding a protein related to the human β-amyloid protein precursor. Proc Natl Acad Sci U S A 1993; 90:12045–9.

    PubMed  CAS  Google Scholar 

  59. Iijima K, Lee DS, Okutsu J, et al. cDNA isolation of Alzheimer’s amyloid precursor protein from cholinergic nerve terminals of the electric organ of the electric ray. Biochem J 1998;330:29–33.

    PubMed  CAS  Google Scholar 

  60. Okado H, Okamoto H. A Xenopus homologue of the human β-amyloid precursor protein: developmental regulation of its gene expression. Biochem Biophys Res Commun 1992;189:1561–8.

    PubMed  CAS  Google Scholar 

  61. Rosen DR, Martin-Morris L, Luo LQ, White K. A Drosophila gene encoding a protein resembling the human beta-amyloid protein precursor. Proc Natl Acad Sci U S A 1989;86:2478–82.

    PubMed  CAS  Google Scholar 

  62. De Strooper B, Annaert W. Proteolytic processing and cell biological functions of the amyloid precursor protein. J Cell Sci 2000;113:1857–70.

    PubMed  Google Scholar 

  63. Anderson JP, Chen Y, Kim KS, Robakis NK. An alternative secretase cleavage produces soluble Alzheimer amyloid precursor protein containing a potentially amyloidogenic sequence. J Neurochem 1992;59:2328–31.

    Article  PubMed  CAS  Google Scholar 

  64. LeBlanc AC, Papadopoulos M, Bélair C, et al. Processing of amyloid precursor protein in human primary neuron and astrocyte cultures. J Neurochem 1997;68:1183–90.

    Article  PubMed  CAS  Google Scholar 

  65. Ikezu T, Trapp BD, Song KS, et al. Caveolae, plasma membrane microdomains for alpha-secretase-mediated processing of the amyloid precursor protein. J Biol Chem 1998;273:10485–95.

    PubMed  CAS  Google Scholar 

  66. Buxbaum JD, Liu KN, Luo YX, et al. Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 1998;273:27765–7.

    PubMed  CAS  Google Scholar 

  67. Lammich S, Kojro E, Postina R, et al. Constitutive and regulated α-secretase cleavage of Alzheimer’s amyloid precursor protein by a disintegrin metalloprotease. Proc Natl Acad Sci U S A 1999;96:3922–7.

    PubMed  CAS  Google Scholar 

  68. Asai M, Hattori C, Szabo B, et al. Putative function of ADAM9, ADAM10, and ADAM17 as APP alphasecretase. Biochem Biophys Res Commun 2003; 301:231–5.

    PubMed  CAS  Google Scholar 

  69. Allinson TM, Parkin ET, Turner AJ, Hooper NM. ADAMs family members as amyloid precursor protein alpha-secretases. J Neurosci Res 2003;74:342–52.

    PubMed  CAS  Google Scholar 

  70. De Strooper B, Umans L, Van Leuven F, Van Den Berghe H. Study of the synthesis and secretion of normal and artificial mutants of murine amyloid precursor protein (APP): cleavage of APP occurs in a late compartment of the default secretion pathway. J Cell Biol 1993;121:295–304.

    PubMed  Google Scholar 

  71. Sambamurti K, Shioi J, Anderson JP, et al. Evidence for intracellular cleavage of the Alzheimer’s amyloid precursor in PC12 cells. J Neurosci Res 1992;33:319–29.

    PubMed  CAS  Google Scholar 

  72. Haass C, Hung AY, Schlossmacher MG, et al. β-amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J Biol Chem 1993;268:3021–4.

    PubMed  CAS  Google Scholar 

  73. Hussain I, Powell D, Howlett DR, et al. Identification of a novel aspartic protease (Asp 2) as β-secretase. Mol Cell Neurosci 1999;14:419–27.

    PubMed  CAS  Google Scholar 

  74. Vassar R, Bennett BD, Babu-Khan S, et al. Beta-secretase cleavage of Alzheimer’s amyloid precursor protein by the transmembrane aspartic protease BACE. Science 1999;286:735–41.

    PubMed  CAS  Google Scholar 

  75. Sinha S, Anderson JP, Barbour R, et al. Purification and cloning of amyloid precursor protein β-secretase from human brain. Nature 1999;402:537–40.

    PubMed  CAS  Google Scholar 

  76. Yan R, Bienkowski MJ, Shuck ME, et al. Membraneanchored aspartyl protease with Alzheimer’s disease β-secretase activity. Nature 1999;402:533–7.

    PubMed  CAS  Google Scholar 

  77. Busciglio J, Gabuzda DH, Matsudaira P, Yankner BA. Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc Natl Acad Sci U S A 1993;90:2092–6.

    PubMed  CAS  Google Scholar 

  78. Seubert P, Vigo-Pelfrey C, Esch F, et al. Isolation and quantification of soluble Alzheimer’s β-peptide from biological fluids. Nature 1992;359:325–7.

    PubMed  CAS  Google Scholar 

  79. Estus S, Golde TE, Kunishita T, et al. Potentially amyloidogenic, carboxyl-terminal derivatives of the amyloid protein precursor. Science 1992;255:726–8.

    PubMed  CAS  Google Scholar 

  80. Golde TE, Estus S, Younkin LH, et al. Processing of the amyloid protein precursor to potentially amyloidogenic derivatives. Science 1992;255:728–30.

    PubMed  CAS  Google Scholar 

  81. Bennett BD, Babu-Khan S, Loeloff R, et al. Expression analysis of BACE2 in brain and peripheral tissues. J Biol Chem 2000;275:20647–51.

    PubMed  CAS  Google Scholar 

  82. Wen Y, Onyewuchi O, Yang S, et al. Increased betasecretase activity and expression in rats following transient cerebral ischemia. Brain Res 2004;1009:1–8.

    PubMed  CAS  Google Scholar 

  83. Haass C. Take five-BACE and the gamma-secretase quartet conduct Alzheimer’s amyloid b-peptide generation. EMBO J 2004;11:483–8.

    Google Scholar 

  84. Pollwein P, Masters CL, Beyreuther K. The expression of the amyloid precursor protein (APP) is regulated by two GC-elements in the promoter. Nucleic Acids Res 1992;20:63–8.

    PubMed  CAS  Google Scholar 

  85. von Koch CS, Lahiri DK, Mammen AL, et al. The mouse APLP2 gene-chromosomal localization and promoter characterization. J Biol Chem 1995;270: 25475–80.

    Google Scholar 

  86. Mattson MP, Cheng B, Culwell AR, et al. Evidence for excitoprotective and intraneuronal calcium-regulating roles for secreted forms of the beta-amyloid precursor protein. Neuron 1993;10:243–54.

    PubMed  CAS  Google Scholar 

  87. Schubert D, Jin LW, Saitoh T, Cole G. The regulation of amyloid β protein precursor secretion and its modulatory role in cell adhesion. Neuron 1989;3:689–94.

    PubMed  CAS  Google Scholar 

  88. Van Nostrand WE. Zinc (II) selectively enhances the inhibition of coagulation factor XIa by protease nexin-2/amyloid beta-protein precursor. Thromb Res 1995;78:43–53.

    PubMed  Google Scholar 

  89. Smith RP, Higuchi DA, Broze GJ, Jr. Platelet coagulation factor XIa-inhibitor, a form of Alzheimer amyloid precursor protein. Science 1990;248:1126–8.

    PubMed  CAS  Google Scholar 

  90. Henry A, Li QX, Galatis D, et al. Inhibition of platelet activation by the Alzheimer’s disease amyloid precursor protein. Br J Haematol 1998;103:402–15.

    PubMed  CAS  Google Scholar 

  91. Schubert D, Behl C. The expression of amyloid beta protein precursor protects nerve cells from betaamyloid and glutamate toxicity and alters their interaction with the extracellular matrix. Brain Res 1993; 629:275–82.

    PubMed  CAS  Google Scholar 

  92. Furukawa K, Sopher BL, Rydel RE, et al. Increased activity-regulating and neuroprotective efficacy of alpha-secretase-derived secreted amyloid precursor protein conferred by a C-terminal heparin-binding domain. J Neurochem 1996;67:1882–96.

    Article  PubMed  CAS  Google Scholar 

  93. Smith-Swintosky VL, Pettigrew LC, Craddock SD, et al. Secreted forms of beta-amyloid precursor protein protect against ischemic brain injury. J Neurochem 1994;63:781–4.

    Article  PubMed  CAS  Google Scholar 

  94. McKenzie JE, Gentleman SM, Roberts GW, et al. Increased numbers of βAPP-immunoreactive neurones in the entorhinal cortex after head injury. Neuroreport 1994;6:161–4.

    PubMed  CAS  Google Scholar 

  95. Nakamura Y, Takeda M, Niigawa H, et al. Amyloid β-protein precursor deposition in rat hippocampus lesioned by ibotenic acid injection. Neurosci Lett 1992;136:95–8.

    PubMed  CAS  Google Scholar 

  96. Ciallella JR, Ikonomovic MD, Paljug WR, et al. Changes in expression of amyloid precursor protein and interleukin-1beta after experimental traumatic brain injury in rats. J Neurotrauma 2002;19:1555–67.

    PubMed  Google Scholar 

  97. Card JP, Meade RP, Davis LG. Immunocytochemical localization of the precursor protein for β-amyloid in the rat central nervous system. Neuron 1988;1:835–46.

    PubMed  CAS  Google Scholar 

  98. Masliah E, Mallory M, Ge N, Saitoh T. Amyloid precursor protein is localized in growing neurites of neonatal rat brain. Brain Res 1992;593:323–8.

    PubMed  CAS  Google Scholar 

  99. Storey E, Beyreuther K, Masters CL. Alzheimer’s disease amyloid precursor protein on the surface of cortical neurons in primary culture co-localizes with adhesion patch components. Brain Res 1996;735:217–31.

    PubMed  CAS  Google Scholar 

  100. Löffler J, Huber G. β-Amyloid precursor protein isoforms in various rat brain regions and during brain development. J Neurochem 1992;59:1316–24.

    PubMed  Google Scholar 

  101. Clarris HJ, Key B, Beyreuther K, et al. 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.

    PubMed  CAS  Google Scholar 

  102. Koo EH, Park L, Selkoe DJ. Amyloid β-protein as a substrate interacts with extracellular matrix to promote neurite outgrowth. Proc Natl Acad Sci U S A 1993;90:4748–52.

    PubMed  CAS  Google Scholar 

  103. Milward E, Papadopoulos R, Fuller SJ, et al. The amyloid protein precursor of Alzheimer’s disease is a mediator of the effects of nerve growth factor on neurite outgrowth. Neuron 1992;9:129–37.

    PubMed  CAS  Google Scholar 

  104. Mok SS, Sberna G, Heffernan D, et al. Expression and analysis of heparin-binding regions of the amyloid precursor protein of Alzheimer’s disease. FEBS Lett 1997;415:303–7.

    PubMed  CAS  Google Scholar 

  105. Qiu WQ, Ferreira A, Miller C, et al. J. Cell-surface beta-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoformdependent manner. J Neurosci 1995;15:2157–67.

    PubMed  CAS  Google Scholar 

  106. Ribaut-Barassin C, Dupont JL, Haeberle AM, et al. Alzheimer’s disease proteins in cerebellar and hippocampal synapses during postnatal development and aging of the rat. Neuroscience 2003;120: 405–23.

    PubMed  CAS  Google Scholar 

  107. Bush AI, Martins RN, Rumble B, et al. The amyloid precursor protein of Alzheimer’s disease is released by human platelets. J Biol Chem 1990;265:15977–83.

    PubMed  CAS  Google Scholar 

  108. Evin G, Zhu A, Holsinger RM, et al. Proteolytic processing of the Alzheimer’s disease amyloid precursor protein in brain and platelets. J Neurosci Res 2003;74:386–92.

    PubMed  CAS  Google Scholar 

  109. Skovronsky DM, Lee VM, Pratico D. Amyloid precursor protein and amyloid beta peptide in human platelets. Role of cyclooxygenase and protein kinase C. J Biol Chem 2001;276:17036–43.

    PubMed  CAS  Google Scholar 

  110. Storey E, Cappai R. The amyloid precursor protein of Alzheimer’s disease and the Abeta peptide. Neuropathol Appl Neurobiol 1999;25:81–97.

    PubMed  CAS  Google Scholar 

  111. Nishimoto I, Okamoto T, Matsuura Y, et al. Alzheimer amyloid protein precursor complexes with brain GTP-binding protein G. Nature 1993; 362:75–9.

    PubMed  CAS  Google Scholar 

  112. Okamoto T, Takeda S, Murayama Y, et al. Liganddependent G protein coupling function of amyloid transmembrane precursor. J Biol Chem 1995;270: 4205–8.

    PubMed  CAS  Google Scholar 

  113. Giambarella U, Yamatsuji T, Okamoto T, et al. G protein betagamma complex-mediated apoptosis by familial Alzheimer’s disease mutant of APP. EMBO J 1997;16:4897–907.

    PubMed  CAS  Google Scholar 

  114. Mahlapuu R, Viht K, Balaspiri L, et al. Amyloid precursor protein carboxy-terminal fragments modulate G-proteins and adenylate cyclase activity in Alzheimer’s disease brain. Brain Res Mol Brain Res 2003;117:73–82.

    PubMed  CAS  Google Scholar 

  115. Yamatsuji T, Matsui T, Okamoto T, et al. G proteinmediated neuronal DNA fragmentation induced by familial Alzheimer’s disease-associated mutants of APP. Science 1996;272:1349–52.

    PubMed  CAS  Google Scholar 

  116. Garcia-Jimenez A, Cowburn RF, Ohm TG, et al. Loss of stimulatory effect of guanosine triphosphate on [(35)S]GTPgammaS binding correlates with Alzheimer’s disease neurofibrillary pathology in entorhinal cortex and CA1 hippocampal subfield. J Neurosci Res 2002;67:388–98.

    PubMed  CAS  Google Scholar 

  117. Kerr ML, Small DH. Cytoplasmic domain of the beta-amyloid protein precursor of Alzheimer’s disease: function, regulation of proteolysis, and implications for drug development. J Neurosci Res 2005;80:151–9.

    PubMed  CAS  Google Scholar 

  118. Kimberly WT, Zheng JB, Guenette SY, Selkoe DJ. The intracellular domain of the beta-amyloid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner. J Biol Chem 2001;276:40288–92.

    PubMed  CAS  Google Scholar 

  119. Perkinton MS, Standen CL, Lau KF, et al. The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to stimulate Fe65/amyloid precursor protein nuclear signaling. J Biol Chem 2004;279: 22084–91.

    PubMed  CAS  Google Scholar 

  120. Pietrzik CU, Yoon IS, Jaeger S, et al. FE65 constitutes the functional link between the low-density lipoprotein receptor-related protein and the amyloid precursor protein. J Neurosci 2004;24:4259–65.

    PubMed  CAS  Google Scholar 

  121. von der Kammer H, Loffler C, Hanes J, et al. The gene for the amyloid precursor-like protein APLP2 is assigned to human chromosome 11q23-q25. Genomics 1994;10:308–11.

    Google Scholar 

  122. Wasco W, Gurubhagavatula S, Paradis MD, et al. Isolation and characterization of APLP2 encoding a homologue of the Alzheimer’s associated amyloid β protein precursor. Nat Genet 1993;5:95–100.

    PubMed  CAS  Google Scholar 

  123. Sandbrink R, Masters CL, Beyreuther K. APP gene family. Alternative splicing generates functionally related isoforms. Ann N Y Acad Sci 1996;777:281–7.

    PubMed  CAS  Google Scholar 

  124. Wasco W, Bupp K, Magendantz M, et al. Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer’s disease-associated amyloid β protein precursor. Proc Natl Acad Sci U S A 1992;89:10758–62.

    PubMed  CAS  Google Scholar 

  125. Collin RWJ, van Strein D, Leunissen JAM, Marten GJM. Identification and expression of the first nonmammalian amyloid-β precursor-like protein APLP2 in the amphibian Xenopus laevis. Eur J Biochem 2004;271:1906–12.

    PubMed  CAS  Google Scholar 

  126. Slunt HH, Thinakaran G, Von Koch C, et al. Expression of a ubiquitous, cross-reactive homologue of the mouse β-amyloid precursor protein (APP). J Biol Chem 1994;269:2637–44.

    PubMed  CAS  Google Scholar 

  127. Thinakaran G, Kitt CA, Roskams AJ, et al. Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci 1995;15:6314–26.

    PubMed  CAS  Google Scholar 

  128. Cappai R, Mok SS, Galatis D, et al. Recombinant human amyloid precursor-like protein 2 (APLP2) expressed in the yeast Pichia pastoris can stimulate neurite outgrowth. FEBS Lett 1999;442:95–8.

    PubMed  CAS  Google Scholar 

  129. Holback S, Adlerz L, Iverfeldt K. Increased processing of APLP2 and APP with concomitant formation of APP intracellular domains in BDNF and retinoic acid-differentiated human neuroblastoma cells. J Neurochem 2005;95:1059–68.

    PubMed  CAS  Google Scholar 

  130. Thinakaran G, Kitt CA, Roskams AJI, et al. Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci 1995;15:6314–26.

    PubMed  CAS  Google Scholar 

  131. Guo J, Thinakaran G, Guo Y, et al. A role for amyloid precursor-like protein 2 in corneal epithelial wound healing. Invest Ophthalmol Vis Sci 1998; 39:292–300.

    PubMed  CAS  Google Scholar 

  132. Kummer C, Wehner C, Quast T, et al. Expression and potential function of amyloid precursor proteins during cutaneous wound repair. Exp Cell Res 2002; 280:222–32.

    PubMed  CAS  Google Scholar 

  133. Beckman M, Iverfeldt K. Increased gene expression of β-amyloid precursor protein and its homologues APLP1 and APLP2 in human neuroblastoma cells in response to retinoic acid. Neurosci Lett 1997; 221:73–6.

    PubMed  CAS  Google Scholar 

  134. White AR, Zheng H, Galatis D, et al. Survival of cultured neurons from amyloid precursor protein knock-out mice against Alzheimer’s amyloid-beta toxicity and oxidative stress. J Neurosci 1998; 18:6207–17.

    PubMed  CAS  Google Scholar 

  135. White AR, Maher F, Brazier MW, et al. Diverse fibrillar peptides directly bind the Alzheimer’s amyloid precursor protein and amyloid precursor-like protein 2 resulting in cellular accumulation. Brain Res 2003;966:231–44.

    PubMed  CAS  Google Scholar 

  136. Hanes J, von der Kammer H, Kristjansson GI, Scheit KH. The complete cDNA coding sequence for the mouse CDEI binding protein. Biochim Biophys Acta 1993;1216:154–6.

    PubMed  CAS  Google Scholar 

  137. Blangy A, Vidal F, Cuzin F, et al. CDEBP, a sitespecific DNA-binding protein of the’ APP-like’ family, is required during the early development of the mouse. J Cell Sci 1995;108:675–83.

    PubMed  CAS  Google Scholar 

  138. Rassoulzadegan M, Yang YH, Cuzin F. APLP2, a member of the Alzheimer precursor protein family, is required for correct genomic segregation in dividing mouse cells. EMBO J 1998;17:4647–56.

    PubMed  CAS  Google Scholar 

  139. Wasco W, Brook JD, Tanzi RE. The amyloid precursor-like protein (APLP) gene maps to the long arm of human chromosome 19. Genomics 1993; 15:237–9.

    PubMed  CAS  Google Scholar 

  140. Lyckman AW, Confaloni AM, Thinakaran G, et al. Post-translational processing and turnover kinetics of presynaptically targeted amyloid precursor superfamily proteins in the central nervous system. J Biol Chem 1998;273:11100–6.

    PubMed  CAS  Google Scholar 

  141. Suzuki T, Ando K, Isohara T, et al. Phosphorylation of Alzheimer β-amyloid precursor-like proteins. Biochemistry 1997;36:4643–9.

    PubMed  CAS  Google Scholar 

  142. Scheinfeld MH, Ghersi E, Laky K, et al. Processing of β-amyloid precursor-like protein-1 and-2 by γ-secretase regulates transcription. J Biol Chem 2002;277:44195–201.

    PubMed  CAS  Google Scholar 

  143. Paliga K, Peraus G, Kreger S, et al. Human amyloid precursor-like protein 1-cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid. Eur J Biochem 1997;250:354–63.

    PubMed  CAS  Google Scholar 

  144. Lorent K, Overbergh L, Moechars D, et al. Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/ low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. Neuroscience 1995;65:1009–25.

    PubMed  CAS  Google Scholar 

  145. Kim TW, Wu K, Xu JL, et al. Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density. Mol Brain Res 1995; 32:36–44.

    PubMed  CAS  Google Scholar 

  146. Zheng H, Jiang M, Trumbauer ME, et al. beta-Amyloid precursor protein-deficient mice show reactive gliosis and decreased locomotor activity. Cell 1995;81:525–31.

    PubMed  CAS  Google Scholar 

  147. Phinney AL, Calhoun ME, Wolfer DP, et al. No hippocampal neuron or synaptic bouton loss in learning-impaired aged beta-amyloid precursor protein-null mice. Neuroscience 1999;90:1207–16.

    PubMed  CAS  Google Scholar 

  148. Dawson GR, Seabrook GR, Zheng H, et al. Agerelated cognitive deficits, impaired long-term potentiation and reduction in synaptic marker density in mice lacking the β-Amyloid precursor protein. Neuroscience 1999;90:1–13.

    PubMed  CAS  Google Scholar 

  149. Seabrook GR, Smith DW, Bowery BJ, et al. Mechanisms contributing to the deficits in hippocampal synaptic plasticity in mice lacking amyloid precursor protein. Neuropharmacology 1999;38:349–59.

    PubMed  CAS  Google Scholar 

  150. Stephan A, Davis S, Salin H, et al. Age-dependent differential regulation of genes encoding APP and alpha-synuclein in hippocampal synaptic plasticity. Hippocampus 2002;12:55–62.

    PubMed  CAS  Google Scholar 

  151. Muller U, Cristina N, Li ZW, et al. Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene. Cell 1994;79:755–65.

    PubMed  CAS  Google Scholar 

  152. Tremml P, Lipp HP, Müller U, et al. Neurobehavioral development, adult openfield exploration and swimming navigation learning in mice with a modified β-amyloid precursor protein gene. Behav Brain Res 1998;95:65–76.

    PubMed  CAS  Google Scholar 

  153. Steinbach JP, Muller U, Leist M, et al. Hypersensitivity to seizures in beta-amyloid precursor protein deficient mice. Cell Death Differ 1998; 5:858–66.

    PubMed  CAS  Google Scholar 

  154. Magara F, Müller U, Li ZW, et al. Genetic background changes the pattern of forebrain commissure defects in transgenic mice underexpressing the β-amyloid-precursor protein. Proc Natl Acad Sci U S A 1999;96:4656–61.

    PubMed  CAS  Google Scholar 

  155. Perez RG, Zheng H, Van der Ploeg LHT, Koo EH. The β-amyloid precursor protein of Alzheimer’s disease enhances neuron viability and modulates neuronal polarity. J Neurosci 1997;17:9407–14.

    PubMed  CAS  Google Scholar 

  156. Harper SJ, Bilsland JG, Shearman MS, et al. Mouse cortical neurones lacking APP show normal neurite outgrowth and survival responses in vitro. Neuroreport 1998;9:3053–7.

    PubMed  CAS  Google Scholar 

  157. Heber S, Herms J, Gajic V, et al. Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci 2000;20:7951–63.

    PubMed  CAS  Google Scholar 

  158. Lorenzo A, Yuan M, Zhang Z, et al. Amyloid beta interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer’s disease. Nat Neurosci 2000;3:460–4.

    PubMed  CAS  Google Scholar 

  159. McNamara MJ, Ruff CT, Wasco W, et al. Immunohistochemical and in situ analysis of amyloid precursor-like protein-1 and amyloid precursor-like protein-2 expression in Alzheimer’s disease and aged control brains. Brain Res 1998;804:45–51.

    PubMed  CAS  Google Scholar 

  160. von Koch CS, Zheng H, Chen H, et al. Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging 1997;18:661–9.

    Google Scholar 

  161. Wang P, Yang G, Mosier DR, et al. Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci 2005;25:1219–25.

    PubMed  CAS  Google Scholar 

  162. Torroja L, Luo L, White K. APPL, the Drosophila member of the APP-family, exhibits differential trafficking and processing in CNS neurons. J Neurosci 1996;16:4638–50.

    PubMed  CAS  Google Scholar 

  163. Torroja L, Packard M, Gorczyca M, White K, Budnik V. The Drosophila beta-amyloid precursor protein homolog promotes synapse differentiation at the neuromuscular junction. J Neurosci 1999; 19:7793–803.

    PubMed  CAS  Google Scholar 

  164. Huang X, Atwood CS, Hartshorn MA, et al. The Aß peptide of Alzheimer’s disease directly produces hydrogen peroxide through metal ion reduction. Biochemistry 1999;38:7609–16.

    PubMed  CAS  Google Scholar 

  165. Huang X, Cuajungco MP, Atwood CS, et al. Cu(II) potentiation of Alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction. J Biol Chem 1999; 274:37111–6.

    PubMed  CAS  Google Scholar 

  166. Rae TD, Schmidt PJ, Pufahl RA, et al. Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. Science 1999;284:805–8.

    PubMed  CAS  Google Scholar 

  167. Bellingham SA, Ciccotosto GD, Needham BE, et al. Gene knockout of amyloid precursor protein and amyloid precursor-like protein-2 increases cellular copper levels in primary mouse cortical neurons. J Neurochem 2004;91:423–8.

    PubMed  CAS  Google Scholar 

  168. Treiber C, Simons A, Strauss M, et al. Clioquinol mediates copper uptake and counteracts copper efflux activities of the amyloid precursor protein of Alzheimer’s disease. J Biol Chem 2004;279:51958–64.

    PubMed  CAS  Google Scholar 

  169. Cappai R, Cheng F, Ciccotosto GD, et al. The amyloid precursor protein (APP) of Alzheimer’s disease and its paralog, APLP2, modulate the Cu/Zn-nitric oxide-catalyzed degradation of glypican-1 heparan sulfate in vivo. J Biol Chem 2005;280:13913–20.

    PubMed  CAS  Google Scholar 

  170. Williamson TG, Mok SS, Henry A, et al. Secreted glypican binds to the amyloid precursor protein of Alzheimer’s disease (APP) and inhibits APPinduced neurite outgrowth. J Biol Chem 1996; 271:31215–21.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, and Centre for Neuroscience, The University of Melbourne, Melbourne, VIC, Australia

    Roberto Cappai BSc(Hons), PhD

  2. Mental Health Research Institute, Parkville, VIC, Australia

    Roberto Cappai BSc(Hons), PhD, B. Elise Needham PhD & Giuseppe D. Ciccotosto BSc, PhD

  3. Department of Pathology, The University of Melbourne, Parkville, VIC, Australia

    B. Elise Needham PhD & Giuseppe D. Ciccotosto BSc, PhD

Authors
  1. Roberto Cappai BSc(Hons), PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Elise Needham PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giuseppe D. Ciccotosto BSc, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Research and Development, Ocean Nutrition Canada, Dartmouth, Nova Scotia, Canada

    Colin J. Barrow BSc (Hons),PhD, MBA (Vice President) (Vice President)

  2. Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia

    David H. Small BSc, PhD (Associate Professorial Fellow) (Associate Professorial Fellow)

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag London Limited

About this chapter

Cite this chapter

Cappai, R., Elise Needham, B., Ciccotosto, G.D. (2007). The Function of the Amyloid Precursor Protein Family. In: Barrow, C.J., Small, D.H. (eds) Abeta Peptide and Alzheimer’s Disease. Springer, London. https://doi.org/10.1007/978-1-84628-440-3_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-84628-440-3_3

  • Publisher Name: Springer, London

  • Print ISBN: 978-1-85233-961-6

  • Online ISBN: 978-1-84628-440-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation