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Generation of antibodies specific for β-amyloid by vaccination of patients with Alzheimer disease

Nature Medicine volume 8, pages 1270–1275 (2002)Cite this article

Abstract

To characterize antibodies produced in humans in response to Aβ42 vaccination, we carried out immunohistochemical examinations of the brains of both transgenic mice and human patients with β-amyloid pathology. We collected sera from patients with Alzheimer disease who received a primary injection of pre-aggregated Aβ42 followed by one booster injection in a placebo-controlled study. Antibodies in immune sera recognized β-amyloid plaques, diffuse Aβ deposits and vascular β-amyloid in brain blood vessels. The antibodies did not cross-react with native full-length β-amyloid precursor protein or its physiological derivatives, including soluble Aβ42. These findings indicate that vaccination of AD patients with Aβ42 induces antibodies that have a high degree of selectivity for the pathogenic target structures. Whether vaccination to produce antibodies against β-amyloid will halt the cognitive decline in AD will depend upon clinical assessments over time.

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Figure 1: Antibodies against β-amyloid generated in human sera in response to vaccination with Aβ42 stain β-amyloid plaques and vascular amyloid in brains of APPSw×PS1M146L mice.
Figure 2: Immune sera do not cross-react with full-length APP or its physiologic derivatives.
Figure 3: Antibodies against β-amyloid in human immune sera stain β-amyloid plaques, diffuse Aβ deposits and vascular amyloid in human brains.
Figure 4: Vaccination-induced antibodies against β-amyloid in human CSF recognize β-amyloid plaques and vascular amyloid in brains of APPSw×PS1M146L mice.

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Acknowledgements

We thank D. Schenk, R. Black and A. Aguzzi for critical reading of the manuscript; A. Fontana for helpful comments; E. Garcia, C. Wilde, A. Walther, and R. Schmid for clinical study support; J. Tracy and J. Bosset for technical support; M. Jaber for artwork; the Netherlands Brain Research Institute, A. Deng, M. Frosch and A. Aguzzi for brain tissue samples; K. Duff and K. Hsiao-Ashe for transgenic mouse lines; and Evotec NeuroSciences GmbH for antibodies. This study was funded in parts by the National Center of Competence in Research on Neural Plasticity and Repair, the EU DIADEM programme on Diagnosis of Dementia, the Stammbach Foundation and the University of Zurich.

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  1. Christoph Hock and Uwe Konietzko: C.H. and U.K. contributed equally to this study.

Authors and Affiliations

  1. Division of Psychiatry Research, University of Zurich, Zurich, Switzerland

    Christoph Hock, Uwe Konietzko, Andreas Papassotiropoulos, Axel Wollmer, Johannes Streffer, Ruth C. von Rotz, Gabriela Davey, Eva Moritz & Roger M. Nitsch

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Correspondence to Roger M. Nitsch.

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Hock, C., Konietzko, U., Papassotiropoulos, A. et al. Generation of antibodies specific for β-amyloid by vaccination of patients with Alzheimer disease. Nat Med 8, 1270–1275 (2002). https://doi.org/10.1038/nm783

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