Glycosylation changes in Alzheimer's disease as revealed by a proteomic approach

Neurosci Lett. 2004 Sep 2;367(2):235-40. doi: 10.1016/j.neulet.2004.06.013.

Abstract

Glycosylation influences the biological activity of proteins and affects their folding and stability. Because aberrant glycosylation is associated with Alzheimer's disease (AD), we applied proteome analysis together with Pro-Q Emerald 300 glycoprotein staining to investigate changes in glycosylated cytosolic proteins in AD and control brain. Frontal cortex proteins from 10 AD patients and 7 non-demented controls were subjected to separation by two-dimensional gel electrophoresis and subsequently stained with carbohydrate-specific Pro-Q Emerald 300 dye. Changes in glycosylation of separated proteins were quantified, and proteins of interest identified by mass spectrometry. Approximately 30% of all detectable proteins in the human frontal cortex appeared glycosylated, including heat shock cognate 71 stress protein and beta isoform of creatine kinase. The glycosylation of collapsin response mediator protein 2 (CRMP-2) and an unknown protein was reduced in AD, while the glycosylation of glial fibrillary acidic protein was increased. CRMP-2 regulates the assembly and polymerization of microtubules and is associated with neurofibrillary tangles in AD. Aberrant glycosylations in AD may help understand the mechanisms of neurodegenerative diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / metabolism*
  • Brain Chemistry
  • Coloring Agents
  • Electrophoresis, Gel, Two-Dimensional / methods
  • Female
  • Frontal Lobe / metabolism*
  • Glial Fibrillary Acidic Protein / metabolism
  • Glycoproteins / metabolism*
  • Glycosylation
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Nerve Tissue Proteins / metabolism
  • Proteomics / methods*

Substances

  • Coloring Agents
  • Glial Fibrillary Acidic Protein
  • Glycoproteins
  • Intercellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • collapsin response mediator protein-2