Cytotoxicity mediated by conditional expression of a carboxyl-terminal derivative of the beta-amyloid precursor protein

Brain Res Mol Brain Res. 1994 Oct;26(1-2):207-17. doi: 10.1016/0169-328x(94)90092-2.


The beta amyloid peptide which accumulates within the brains of patients with Alzheimer's disease (AD) is proteolytically derived from a precursor protein (beta PP). We established and characterized four stably transformed human neuroblastoma cell lines which conditionally expressed a partial beta PP fusion protein (amino-17 residues+carboxyl-99 residues; S beta C). Conditional expression of S beta C was achieved using a tetracycline-responsive promoter system. Expression of this fusion protein in one of the cell lines resulted in pronounced cytotoxicity. Addition of n6,O2'-dibutyryl adenosine 3',5'-cyclic monophosphate and/or fetal bovine serum to the culture medium of this cell line further elevated the level of S beta C expression and enhanced the associated cytotoxicity. Conditioned medium, acquired from cells expressing S beta C, was not cytotoxic. These findings suggest that modulation of beta PP expression and/or metabolism can have cytotoxic consequences. This is the first report of cytotoxic effects mediated by conditional expression of a beta PP derivative. This immortal cell line provides a unique opportunity to screen for complementary DNAs which suppress this toxicity. Such cDNAs could help elucidate the processes underlying S beta C mediated cytotoxicity which in turn could further our understanding of the pathogenesis of AD and could also provide additional candidate genes for various forms of familial AD.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / biosynthesis*
  • Brain / metabolism
  • Bucladesine / pharmacology
  • Cell Line
  • Cell Survival* / drug effects
  • Flow Cytometry
  • Gene Expression / drug effects
  • Humans
  • Neuroblastoma
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins / biosynthesis
  • Restriction Mapping
  • Tetracycline / pharmacology
  • Transfection
  • Tumor Cells, Cultured


  • Amyloid beta-Protein Precursor
  • Recombinant Fusion Proteins
  • Bucladesine
  • Tetracycline