Increased levels of antigen-bound β-amyloid autoantibodies in serum and cerebrospinal fluid of Alzheimer's disease patients

PLoS One. 2013 Jul 18;8(7):e68996. doi: 10.1371/journal.pone.0068996. Print 2013.

Abstract

Recent studies have suggested a protective role of physiological β-amyloid autoantibodies (Aβ-autoantibodies) in Alzheimer's disease (AD). However, the determination of both free and dissociated Aβ-autoantibodies in serum hitherto has yielded inconsistent results regarding their function and possible biomarker value. Here we report the application of a new sandwich enzyme-linked immunosorbent assay (ELISA) for the determination of antigen-bound Aβ-autoantibodies (intact Aβ-IgG immune complexes) in serum and cerebrospinal fluid (CSF) of a total number of 112 AD patients and age- and gender-matched control subjects. Both serum and CSF levels of Aβ-IgG immune complexes were found to be significantly higher in AD patients compared to control subjects. Moreover, the levels of Aβ-IgG complexes were negatively correlated with the cognitive status across the groups, increasing with declining cognitive test performance of the subjects. Our results suggest a contribution of IgG-type autoantibodies to Aβ clearance in vivo and an increased immune response in AD, which may be associated with deficient Aβ-IgG removal. These findings may contribute to elucidating the role of Aβ-autoantibodies in AD pathophysiology and their potential application in AD diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / immunology*
  • Amyloid beta-Peptides / immunology*
  • Antibody Specificity
  • Autoantibodies / blood*
  • Autoantibodies / cerebrospinal fluid*
  • Cognition / physiology
  • Enzyme-Linked Immunosorbent Assay / methods*
  • Epitopes / genetics
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid
  • Male
  • Middle Aged
  • Models, Statistical

Substances

  • Amyloid beta-Peptides
  • Autoantibodies
  • Epitopes
  • Immunoglobulin G

Grants and funding

This research was funded as an interdisciplinary project within the WIN-Kolleg (Junior Academy for Young Scholars and Scientists) of the Heidelberg Academy of Sciences, Heidelberg, Germany, awarded to I.-T. Kolassa, M. Manea and C.A.F. von Arnim, by the Zukunftskolleg (I.-T. Kolassa, now alumna, and M. Manea) and Research Center Proteostasis (M. Przybylski), University of Konstanz. I.-T. Kolassa is now at the University of Ulm, F. Thurm is now at the TU Dresden. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.