Increased bisecting and core-fucosylated N-glycans on mutant human amyloid precursor proteins

Glycoconj J. 2008 Nov;25(8):775-86. doi: 10.1007/s10719-008-9140-x. Epub 2008 Jun 3.


Alteration of glycoprotein glycans often changes various properties of the glycoprotein. To understand the significance of N-glycosylation in the pathogenesis of early-onset familial Alzheimer's disease (AD) and in beta-amyloid (Abeta) production, we examined whether the mutations in the amyloid precursor protein (APP) gene found in familial AD affect the N-glycans on APP. We purified the secreted forms of wild-type and mutant human APPs (both the Swedish type and the London type) produced by transfected C17 cells and determined the N-glycan structures of these three recombinant APPs. Although the major N-glycan species of the three APPs were similar, both mutant APPs contained higher contents of bisecting N-acetylglucosamine and core-fucose residues as compared to wild-type APP. These results demonstrate that familial AD mutations in the polypeptide backbone of APP can affect processing of the attached N-glycans; however, whether these changes in N-glycosylation affect Abeta production remains to be established.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Amyloid beta-Protein Precursor / chemistry*
  • Amyloid beta-Protein Precursor / genetics*
  • Amyloid beta-Protein Precursor / metabolism
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Chromatography, Ion Exchange
  • Glycosylation
  • Humans
  • Molecular Sequence Data
  • Mutation*
  • Polysaccharides / chemistry*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism


  • Amyloid beta-Protein Precursor
  • Polysaccharides
  • Recombinant Proteins