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Immune complexes of auto-antibodies against Aβ1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients

Molecular Psychiatry volume 12, pages 601–610 (2007)Cite this article

Abstract

The diagnostic potential of large Aβ-peptide binding particles (LAPs) in the cerebrospinal fluid (CSF) of Alzheimer's dementia (AD) patients and non-AD controls (nAD) was evaluated. LAPs were detected by confocal spectroscopy in both groups with high inter-individual variation in number. Molecular imaging by confocal microscopy revealed that LAPs are heterogeneous superaggregates that could be subdivided morphologically into four main types (LAP1–4). LAP-4 type, resembling a ‘large chain of pearls’, was detected in 42.1% of all nAD controls but it was virtually absent in AD patients. LAP-4 type could be selectively removed by protein A beads, a clear indication that it contained immunoglobulins in addition to beta-amyloid peptides (Aβ1-42). We observed a close correlation between LAPs and immunoglobulin G (IgG) concentration in CSF in controls but not in AD patients. Double labeling of LAPs with anti-Aβ and anti-IgG antibodies confirmed that LAP-4 type consisted of Aβ and IgG aggregates. Our results assign a central role to the immune system in regulating Aβ1-42 homeostasis by clustering this peptide in immunocomplexes.

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Acknowledgements

This work was supported by grants from the German Federal Ministry of Education and Research (Competence Net Dementia, grant 01 GI 0420 to JW, JK, Creutzfeldt-Jacob Disease Net, grant JK 01 GI 0301 to JW, JK and HBPP-NGFN2 01 GR 0447 to JW, PL). Experiments were conducted by AWH and PSD at Experimental Biophysics Group (head: P Schwille) and at Membrane Biophysics Group (head: E Neher), both at the Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany. We thank G Beck from the Laboratory of Clinical Neurochemistry of the University Hospital of Erlangen-Nuremberg for the quantification of immunoglobulins and proteins in CSF. We thank our technician S Paul for expertise comments to the experimental setup and U Reulbach for valuable assistance on statistical calculations.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, University of Erlangen-Nuremberg, Erlangen, Germany

    A W Henkel, T W Groemer, H W Klafki, P Lewczuk, H Esselmann, J Kornhuber & J Wiltfang

  2. Department of Miniaturization, ISAS – Institute for Analytical Science, Dortmund, Germany

    P S Dittrich

  3. Department of Membrane Biophysics, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany

    T W Groemer, E A Lemke & J Klingauf

  4. Institute of Biophysics, BioTec, Technical University Dresden, Dresden, Germany

    P Schwille

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  1. A W Henkel
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Correspondence to J Wiltfang.

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Henkel, A., Dittrich, P., Groemer, T. et al. Immune complexes of auto-antibodies against Aβ1-42 peptides patrol cerebrospinal fluid of non-Alzheimer's patients. Mol Psychiatry 12, 601–610 (2007). https://doi.org/10.1038/sj.mp.4001947

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