Neurobiology of Aging
Volume 30, Issue 8 , Pages 1238-1244 , August 2009

Amyloid precursor protein increases cortical neuron size in transgenic mice

  • Esther S. Oh

      Affiliations

    • Department of Medicine, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • ,
  • Alena V. Savonenko

      Affiliations

    • Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • ,
  • Julie F. King

      Affiliations

    • Department of Medicine, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • ,
  • Stina M. Fangmark Tucker

      Affiliations

    • Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • ,
  • Gay L. Rudow

      Affiliations

    • Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • ,
  • Guilian Xu

      Affiliations

    • Department of Neuroscience, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA
    • ,
  • David R. Borchelt

      Affiliations

    • Department of Neuroscience, University of Florida, 100 Newell Drive, Gainesville, FL 32610, USA
    • ,
  • Juan C. Troncoso

      Affiliations

    • Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • Department of Neurology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA
    • Corresponding Author InformationCorresponding author at: Department of Pathology, The Johns Hopkins University School of Medicine, 558 Ross Research Building, 720 Rutland Avenue, Baltimore, MD 21205, USA. Tel.: +410 955 5165; fax: +410 955 9777.

Received 18 October 2007 ,Revised 13 December 2007 ,Accepted 28 December 2007.

References 

  1. Alpar A, Ueberham U, Bruckner MK, Arendt T, Gartner U. The expression of wild-type human amyloid precursor protein affects the dendritic phenotype of neocortical pyramidal neurons in transgenic mice. Int. J. Dev. Neurosci. 2006;24:133–140
  2. Bondolfi L, Calhoun M, Ermini F, Kuhn HG, Wiederhold KH, Walker L, et al. Amyloid-associated neuron loss and gliogenesis in the neocortex of amyloid precursor protein transgenic mice. J. Neurosci. 2002;22:515–522
  3. Borchelt DR, Davis J, Fischer M, Lee MK, Slunt HH, Ratovitsky T, et al. A vector for expressing foreign genes in the brains and hearts of transgenic mice. Genet. Anal. 1996;13:159–163
  4. Breen KC, Bruce M, Anderton BH. Beta amyloid precursor protein mediates neuronal cell–cell and cell–surface adhesion. J. Neurosci. Res. 1991;28:90–100
  5. Calhoun ME, Wiederhold KH, Abramowski D, Phinney AL, Probst A, Sturchler-Pierrat C, et al. Neuron loss in APP transgenic mice. Nature. 1998;395:755–756
  6. Chen M, Yankner BA. An antibody to beta amyloid and the amyloid precursor protein inhibits cell–substratum adhesion in many mammalian cell types. Neurosci. Lett. 1991;125:223–226
  7. Cooke BM. Steroid-dependent plasticity in the medial amygdala. Neuroscience. 2006;138:997–1005
  8. De Strooper B, Van Leuven F, Van Den Berghe H. The amyloid β protein precursor or proteinase nexin II from mouse is closer related to its human homolog than previously reported. Biochim. Biophys. Acta: Gene Struct. Expr. 1991;1129:141–143
  9. Finch CE. Neuron atrophy during aging: programmed or sporadic?. Trends Neurosci. 1993;16:104–110
  10. Fischer W, Chen KS, Gage FH, Bjorklund A. Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging. Neurobiol. Aging. 1992;13:9–23
  11. Games D, Adams D, Alessandrini R, Barbour R, Berthelette P, Blackwell C, et al. Alzheimer-type neuropathology in transgenic mice overexpressing V717F beta-amyloid precursor protein. Nature. 1995;373:523–527
  12. Han P, Dou F, Li F, Zhang X, Zhang YW, Zheng H, et al. Suppression of cyclin-dependent kinase 5 activation by amyloid precursor protein: a novel excitoprotective mechanism involving modulation of tau phosphorylation. J. Neurosci. 2005;25:11542–11552
  13. Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science. 2002;297:353–356
  14. Hsiao K, Chapman P, Nilsen S, Eckman C, Harigaya Y, Younkin S, et al. Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science. 1996;274:99–102
  15. Irizarry MC, McNamara M, Fedorchak K, Hsiao K, Hyman BT. APPSw transgenic mice develop age-related A beta deposits and neuropil abnormalities, but no neuronal loss in CA1. J. Neuropathol. Exp. Neurol. 1997;56:965–973
  16. Irizarry MC, Soriano F, McNamara M, Page KJ, Schenk D, Games D, et al. Abeta deposition is associated with neuropil changes, but not with overt neuronal loss in the human amyloid precursor protein V717F (PDAPP) transgenic mouse. J. Neurosci. 1997;17:7053–7059
  17. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 2004;13:159–170
  18. Lamb BT, Sisodia SS, Lawler AM, Slunt HH, Kitt CA, Kearns WG, et al. Introduction and expression of the 400 kilobase amyloid precursor protein gene in transgenic mice. Nat. Genet. 1993;5:22–30(corrected)
  19. Lambert MP, Barlow AK, Chromy BA, Edwards C, Freed R, Liosatos M, et al. Diffusible, nonfibrillar ligands derived from Abeta1–42 are potent central nervous system neurotoxins. Proc. Natl. Acad. Sci. U.S.A. 1998;95:6448–6453
  20. Lesne S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, et al. A specific amyloid-beta protein assembly in the brain impairs memory. Nature. 2006;440:352–357
  21. 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;82:4245–4249
  22. Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003;39:409–421
  23. Perez RG, Zheng H, Van der Ploeg LH, Koo EH. The beta-amyloid precursor protein of Alzheimer's disease enhances neuron viability and modulates neuronal polarity. J. Neurosci. 1997;17:9407–9414
  24. Price DL, Sisodia SS. Mutant genes in familial Alzheimer's disease and transgenic models. Annu. Rev. Neurosci. 1998;21:479–505
  25. Price DL, Sisodia SS, Borchelt DR. Genetic neurodegenerative diseases: the human illness and transgenic models. Science. 1998;282:1079–1083
  26. Qiu WQ, Ferreira A, Miller C, Koo EH, Selkoe DJ. Cell-surface beta-amyloid precursor protein stimulates neurite outgrowth of hippocampal neurons in an isoform-dependent manner. J. Neurosci. 1995;15:2157–2167
  27. Riudavets MA, Iacono D, Resnick SM, O’Brien R, Zonderman AB, Martin LJ, et al. Resistance to Alzheimer's pathology is associated with nuclear hypertrophy in neurons. Neurobiol. Aging. 2007;28:1484–1492
  28. Savonenko A, Xu GM, Melnikova T, Morton JL, Gonzales V, Wong MP, et al. Episodic-like memory deficits in the APPswe/PS1dE9 mouse model of Alzheimer's disease: relationships to beta-amyloid deposition and neurotransmitter abnormalities. Neurobiol. Dis. 2005;18:602–617
  29. Selkoe DJ. Alzheimer's disease: genotypes, phenotypes, and treatments. Science. 1997;275:630–631
  30. Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, Kreger S, et al. Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J. 2005;24:3624–3634
  31. Sturchler-Pierrat C, Abramowski D, Duke M, Wiederhold KH, Mistl C, Rothacher S, et al. Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology. Proc. Natl. Acad. Sci. U.S.A. 1997;94:13287–13292
  32. Turner PR, O’Connor K, Tate WP, Abraham WC. Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory. Prog. Neurobiol. 2003;70:1–32
  33. Walsh DM, Klyubin I, Fadeeva JV, Cullen WK, Anwyl R, Wolfe MS, et al. Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature. 2002;416:535–539
  34. West MJ, Slomianka L, Gundersen HJ. Unbiased stereological estimation of the total number of neurons in the subdivisions of the rat hippocampus using the optical fractionator. Anat. Rec. 1991;231:482–497
  35. Zheng H, Koo EH. The amyloid precursor protein: beyond amyloid. Mol. Neurodegener. 2006;1:5

☆ All procedures were conducted according to NIH guide for animal care and approved by the JHU Institutional Animal Care and Use Committee.

PII: S0197-4580(08)00003-1

doi: 10.1016/j.neurobiolaging.2007.12.024

Neurobiology of Aging
Volume 30, Issue 8 , Pages 1238-1244 , August 2009

Article Tools

* Image Usage & Resolution