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Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia

Nature Neuroscience volume 12, pages 1361–1363 (2009)Cite this article

Abstract

In Alzheimer's disease, microglia cluster around β-amyloid deposits, suggesting that these cells are important for amyloid plaque formation, maintenance and/or clearance. We crossed two distinct APP transgenic mouse strains with CD11b-HSVTK mice, in which nearly complete ablation of microglia was achieved for up to 4 weeks after ganciclovir application. Neither amyloid plaque formation and maintenance nor amyloid-associated neuritic dystrophy depended on the presence of microglia.

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Figure 1: Virtually complete microglia ablation in icv GCV-treated APPPS1; TK mice does not alter Aβ plaque load.
Figure 2: Amyloid plaque formation in microglia-ablated APPPS1; TK mice.

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Acknowledgements

This work was supported by grants to M.J. (BMBF-01GI0705), F.L.H. (SFB-TR43, Exc 25 and National Institutes of Neurological Disorders and Stroke R01 NS046006) and P.M.M. (US National Institutes of Health AG017617 and NS045205).

Author information

Author notes

  1. Stefan A Grathwohl and Roland E Kälin: These authors contributed equally to this work.

  2. Frank L Heppner and Mathias Jucker: These authors jointly directed the study.

Authors and Affiliations

  1. Department of Cellular Neurology, Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany

    Stefan A Grathwohl, Tristan Bolmont, Stephan A Kaeser, Jörg Odenthal, Rebecca Radde & Mathias Jucker

  2. German Center for Neurodegenerative Diseases, Tübingen, Germany

    Stefan A Grathwohl, Tristan Bolmont, Stephan A Kaeser, Jörg Odenthal, Rebecca Radde & Mathias Jucker

  3. Graduate School of Cellular and Molecular Neuroscience, University of Tübingen, Tübingen, Germany

    Stefan A Grathwohl

  4. Department of Neuropathology, Charité–Universitätsmedizin Berlin, Berlin, Germany

    Roland E Kälin, Stefan Prokop, Georg Winkelmann & Frank L Heppner

  5. Department of Radiation Oncology, University of Tübingen, Tübingen, Germany

    Therese Eldh

  6. Department of Neurology, Mount Sinai School of Medicine, New York, New York, USA

    Sam Gandy

  7. Department of Pathology, Institute of Neuropathology, University Hospital, Zürich, Switzerland

    Adriano Aguzzi

  8. Novartis Institutes for Biomedical Research, Nervous System Research, Basel, Switzerland

    Matthias Staufenbiel

  9. Nathan Kline Institute, Orangeburg, New York, USA

    Paul M Mathews

  10. Departments of Psychiatry, New York University School of Medicine, New York, New York, USA

    Paul M Mathews

  11. Department of Pathology, University of Tübingen, Tübingen, Germany

    Hartwig Wolburg

Authors
  1. Stefan A Grathwohl
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  2. Roland E Kälin
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  5. Georg Winkelmann
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  6. Stephan A Kaeser
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  7. Jörg Odenthal
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  8. Rebecca Radde
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  9. Therese Eldh
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  10. Sam Gandy
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  11. Adriano Aguzzi
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  12. Matthias Staufenbiel
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  13. Paul M Mathews
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  14. Hartwig Wolburg
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  15. Frank L Heppner
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  16. Mathias Jucker
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Contributions

S.A.G., T.B., S.A.K., J.O., R.R., T.E., P.M.M. and H.W. performed the icv experiments. R.E.K., S.P. and G.W. carried out the oral treatment experiments. A.A., M.S. and S.G. provided mice and/or advice. Experimental design and manuscript preparation were mainly carried out by F.L.H. and M.J.

Corresponding authors

Correspondence to Frank L Heppner or Mathias Jucker.

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Supplementary Figures 1–5 and Supplementary Methods (PDF 3074 kb)

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Grathwohl, S., Kälin, R., Bolmont, T. et al. Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia. Nat Neurosci 12, 1361–1363 (2009). https://doi.org/10.1038/nn.2432

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  • DOI: https://doi.org/10.1038/nn.2432

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