Advertisement

Lymphocyte Amyloid Precursor Protein mRNA Isoforms in Normal Aging and Alzheimer’s Disease

  • Richard P. Ebstein
  • Lubov Nemanov
  • Gregory Lubarski
  • Marina Dano
  • Teres Trevis
  • Amos Korczyn
Part of the GWUMC Department of Biochemistry and Molecular Biology Annual Spring Symposia book series (GWUN)

Abstract

The amyloid precursor protein (APP) molecule is expressed on the surface of most cells including neurons.1 The three major isoforms of APP in brain contain 770, 751 and 695 amino acids, respectively. The two longer forms of the molecule contain a Kunitz-type serine protease inhibitor domain (KPI). These longer isoforms (APP770 and APP751) are the principal species found in non-neuronal cells whereas the shorter APP695 is the major form in differentiated neurons.2 Isoform changes have also been observed in AD and following astrocyte, glial and microglial, cell activation.3 It is still unknown which isoforms of APP and which cell types contribute to β/A4 peptide deposition in AD although a number of different cell types are potential contributors to the amyloid load.

Keywords

Amyloid Precursor Protein Normal Aging Amyloid Precursor Protein Gene Amyloid Load Amyloid Precursor Protein Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    T.E. Golde, T.E.S. Estus, M. Usiak, L.H. Younkin, and S.G. Younkin, Expression of beta amyloid protein precursor mRNAs: Recognition of a novel alteratively spliced form and quantitation in Alzheimer’s disease using PCR. Neuron 4: 253 (1990).PubMedCrossRefGoogle Scholar
  2. 2.
    J.P. Anderson, F.S. Esch, P.S. Keim, K. Sambamurti, I. Lieberburg, and N.K. Robakis, Exact cleavage site of Alzheimer amyloid precursor in neuronal PC-12 cells. Neurosc Lett 128: 126 (1991).CrossRefGoogle Scholar
  3. 3.
    S. Itagaki, P.L. McGeer, H. Akiyama, S. Zhu, and D.J. Selkoe, Relationship of microglia and astrocytes to amyloid deposits of Alzheimer’s disease. J Neuroimmunol 24: 173 (1989).PubMedCrossRefGoogle Scholar
  4. 4.
    T. Horikoshi, K.D. Danenberg, T.H.W. Stadibauer, M. Volkenandt, L.C.C. Shea, K. Aigner, B. Gustavsson, L. Leichman, R. Frosing, M. Ray, N.W. Gibson, C.P. Spears, and P.V. Danenberg, Quantitaton of thymidylate synthetase, dihydrofolate reductase and DT-diaphorase gene expression in human tumors using the polymerase chain reaction. Cancer Research 52: 108 (1992).PubMedGoogle Scholar
  5. 5.
    S. Ledoux, N. Rebai, A. Dagenais, I.T. Shaw, J. Nalbantoglu, R.P. Sekaly, and N.R. Cashman, Amyloid precursor protein in peripheral mononuclear cells is upregulated with cell activation. J Immunol 150: 5566 (1993).PubMedGoogle Scholar
  6. 6.
    S.A. Johnson, T. Mcneill, B. Cordell, and C.E. Finch, Relation of neuronal APP-751/APP-695 mRNA ratio and neuritic plaque density in Alzheimer’s disease. Science 248: 854 (1990).PubMedCrossRefGoogle Scholar
  7. 7.
    G. Konig, J.M. Salbaum, O. Wiestier, W. Lang, H.P. Schmitt, C.L. Masters, and K. Beyreuther, Alternative splicing of the βA4 amyloid gene of Alzheimer’s disease in cortex of control and Alzheimer’s disease patients. Mol Brain Res 9: 259 (1991).PubMedCrossRefGoogle Scholar
  8. 8.
    S. Tanaka, L. Liu, J. Kimura, S. Shiojiri, Y. Takahashi, N. Kitaguchi, S. Nakamura, and K. Ueda, Age-related changes in the proportion of amyloid precursor protein mRNAs in Alzheimer’s disease and other neurological disorders. Mol Brain Res 15: 303 (1992).PubMedCrossRefGoogle Scholar
  9. 9.
    S. Tanaka, S. Nakamura, K. Ueda, M. Kameyama, S. Shiojiri, Y. Takahashi, N. Kitaguchi, and H. Ito, Three types of amyloid protein precursor mRNA in the human brain: their differential expression in Alzheimer’s disease. Biochem Biophys Res Comm 157: 472 (1988).PubMedCrossRefGoogle Scholar
  10. 10.
    H.W. Querfurth, E.M. Wijsman, P.H. St George-Hyslop, and D.J. Selkoe βAPP mRNA transcription is increased in cultured fibroblasts from the familial Alzheimer’s disease-1 family. Mol Brain Res 28: 319 (1995).PubMedCrossRefGoogle Scholar
  11. 11.
    M. Citron, C. Vigo-Pelfrey, D.B. Teplow, C. Miller, D. Schenk, J. Johnston, B. Winblad, N. Venizelos, L. Lannfelt, and D. Selkoe, Excessive production of amyloid beta-amyloid protein by peripheral cells of symptomatic and presymptomatic patients carrying the Swedish familial Alzheimer disease mutaion. Proc Natl Acad Sci (USA) 91: 11993 (1994).CrossRefGoogle Scholar
  12. 12.
    J.A. Johnston, R.F. Cowburn, S. Norgren, B. Wiehager, N. Venizelos, B. Winblad, C. Vigo-Pelfrey, D. Schenk, L. Lannfelt, and C. O’Neill Increased β-amyloid release and levels of amyloid precursor protein (APP) in fibroblast cell lines from family members with the Swedish Alzheimer’s disease APP670/671 mutation. FEBS Lett 354: 274 (1994).PubMedCrossRefGoogle Scholar
  13. 13.
    V.K. Singh, H.H. Fudenberg, and F.R. Brown III, Immunologie dysfunction: simultaneous study of Alzheimer’s and older Down’s syndrome patients. Mech Ageing Dev 37: 257 (1987).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Richard P. Ebstein
    • 1
  • Lubov Nemanov
    • 1
  • Gregory Lubarski
    • 1
  • Marina Dano
    • 2
  • Teres Trevis
    • 2
  • Amos Korczyn
    • 2
  1. 1.Shapiro Molecular Neurobiology LaboratoryS. Herzog Memorial HospitalJerusalemIsrael
  2. 2.Neurology DepartmentTel-Aviv University Medical SchoolIsrael

Personalised recommendations