Neurochemical Research

, Volume 33, Issue 7, pp 1332–1340

Structural and Quantitative Comparison of Cerebrospinal Fluid Glycoproteins in Alzheimer’s Disease Patients and Healthy Individuals

  • Carina Sihlbom
  • Pia Davidsson
  • Magnus Sjögren
  • Lars-Olof Wahlund
  • Carol L. Nilsson
Original Paper

DOI: 10.1007/s11064-008-9588-x

Cite this article as:
Sihlbom, C., Davidsson, P., Sjögren, M. et al. Neurochem Res (2008) 33: 1332. doi:10.1007/s11064-008-9588-x
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Abstract

Glycoproteins in cerebrospinal fluid (CSF) are altered in Alzheimer’s Disease (AD) patients compared to control individuals. We have utilized albumin depletion prior to 2D gel electrophoresis to enhance glycoprotein concentration for image analysis as well as structural glycoprotein determination without glycan release using mass spectrometry (MS). The benefits of a direct glycoprotein analysis approach include minimal sample manipulation and retention of structural details. A quantitative comparison of gel-separated glycoprotein isoforms from twelve AD patients and twelve control subjects was performed with glycoprotein-specific and total protein stains. We have also compared glycoforms in pooled CSF obtained from AD patients and control subjects with mass spectrometry. One isoform of α1-antitrypsin showed decreased glycosylation in AD patients while another glycosylated isoform of an unassigned protein was up-regulated. Protein expression levels of α1-antitrypsin were decreased, while the protein levels of apolipoprotein E and clusterin were increased in AD. No specific glycoform could be specifically assigned to AD.

Keywords

ProteomicsGlycoproteomicsGlycoproteinN-linkedGlycosylationGlycoformIsoformCSFCerebrospinal fluidAlzheimer’s Diseaseα1-antitrypsinApolipoprotein EClusterinHaptoglobinα-1-β-glycoproteinZinc-α-2-glycoprotein2D gel electrophoresis2D-GEAlbumin depletionImage analysisMass spectrometryFT-ICR MSLinear ion trap

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Carina Sihlbom
    • 1
  • Pia Davidsson
    • 2
  • Magnus Sjögren
    • 3
  • Lars-Olof Wahlund
    • 4
  • Carol L. Nilsson
    • 1
    • 5
  1. 1.Department of Medical Chemistry and Cell BiologyInstitute of Biomedicine, Sahlgrenska Academy at Goteborg UniversityGoteborgSweden
  2. 2.Discovery Medicine/EpidemiologyAstraZeneca R&D MölndalMolndalSweden
  3. 3.Translational MedicineOrganon NVOssThe Netherlands
  4. 4.Neurotec Department, Section of Clinical GeriatricsKarolinska Institutet, Karolinska University Hospital in HuddingeStockholmSweden
  5. 5.National High Magnetic Field Laboratory, Florida State UniversityTallahasseeUSA