Release of excess amyloid beta protein from a mutant amyloid beta protein precursor

Science. 1993 Jan 22;259(5094):514-6. doi: 10.1126/science.8424174.


The 4-kilodalton amyloid beta protein (A beta), which forms fibrillar deposits in Alzheimer's disease (AD), is derived from a large protein referred to as the amyloid beta protein precursor (beta APP). Human neuroblastoma (M17) cells transfected with constructs expressing wild-type beta APP or a mutant, beta APP delta NL, recently linked to familial AD were compared. After continuous metabolic labeling for 8 hours, cells expressing beta APP delta NL had five times more of an A beta-bearing, carboxyl terminal, beta APP derivative than cells expressing wild-type beta APP and they released six times more A beta into the medium. Thus this mutant beta APP may cause AD because its processing is altered in a way that releases increased amounts of A beta.

Publication types

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

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amino Acid Sequence
  • Amyloid beta-Peptides / biosynthesis*
  • Amyloid beta-Peptides / genetics
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Base Sequence
  • Cloning, Molecular
  • Humans
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed*
  • Neuroblastoma
  • Oligodeoxyribonucleotides
  • Polymerase Chain Reaction / methods
  • Transfection
  • Tumor Cells, Cultured


  • Amyloid beta-Peptides
  • Amyloid beta-Protein Precursor
  • Oligodeoxyribonucleotides