The amyloid precursor protein of Alzheimer disease is expressed as a 130 kDa polypeptide in various cultured cell types

L. Autilio-Gambetti, A. Morandi, M. Tabaton, B. Schaetzle, D. Kovacs, G. Perry, Barry Greenberg, P. Gambetti

Research output: Contribution to journalArticle

Abstract

The vascular and parenchymal amyloid deposits in Alzheimer disease (AD), normal aging and Down syndrome are mainly composed of a 4 kDa polypeptide (A4), which derives from a larger precursor protein (APP). There is evidence that APP is a transmembrane glycoprotein present in most tissues, but the characteristics of APP in intact cells are not yet known. In order to investigate this issue, we examined the immunoreactivity of fibroblasts of human and nonhuman cell lines with antisera raised to synthetic peptides corresponding to A4 and to two other domains of the APP. All three antisera recognized a 130 kDa polypeptide (APP-130) in immunoblots from all cell lines. In fibroblasts, an additional polypeptide of 228 kDa (APP-228) was recognized by the antiserum to A4. In immunoblots of two dimensional gels, APP-130 showed a pI of 6.2, while APP-228 failed to focus in the pH range of 4.7-7.0. Sequential extractions of cells with buffer and with Triton X-100 indicate that APP-130 is extractable with nonionic detergents at high ionic strength, whereas 228 kDa APP is a cystolic component. Immunofluorescence staining is consistent with an intracellular perinuclear and plasma membrane localization. It is concluded that APP-130 and APP-228 are two forms of the APP which result from extensive posttranslational modifications of a smaller original gene product. It is likely that APP undergoes similar posttranslational modifications in different cell types.

Original languageEnglish (US)
Pages (from-to)94-98
Number of pages5
JournalFEBS Letters
Volume241
Issue number1-2
DOIs
Publication statusPublished - Dec 5 1988
Externally publishedYes

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Keywords

  • (Cell culture)
  • Alzheimer's disease
  • Amyloid
  • Amyloid precursor protein

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Autilio-Gambetti, L., Morandi, A., Tabaton, M., Schaetzle, B., Kovacs, D., Perry, G., ... Gambetti, P. (1988). The amyloid precursor protein of Alzheimer disease is expressed as a 130 kDa polypeptide in various cultured cell types. FEBS Letters, 241(1-2), 94-98. https://doi.org/10.1016/0014-5793(88)81038-X