gms | German Medical Science

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

German Society for Neuropathology and Neuroanatomy

12. - 15.09.2012, Erlangen

57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN)

Reducing alzheimer´s disease β-amyloid and cognitive deficits by manipulating il-12/il-23 signaling

Meeting Abstract

  • presenting/speaker Stefan Prokop - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany
  • Johannes vom Berg - University of Zürich, Institute of Experimental Immunology, Zürich, Switzerland
  • Kelly R. Miller - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany
  • Juliane Obst - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany
  • Roland E. Kälin - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany
  • Ileana Lopategui-Cabezas - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Cuba; Medical University of Havana, Institute of Basic and Preclinical Sciences “Victoria de Girón”, Havana, Cuba
  • Anja Wegner - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany
  • Florian Mair - University of Zürich, Institute of Experimental Immunology, Zürich, Switzerland
  • Burkhard Becher - University of Zürich, Institute of Experimental Immunology, Zürich, Switzerland
  • Frank L. Heppner - Charite-Universitätsmedizin Berlin, Department of Neuropathology, Berlin, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 57th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Erlangen, 12.-15.09.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. Doc12dgnnPP4.8

DOI: 10.3205/12dgnn085, URN: urn:nbn:de:0183-12dgnn0851

Published: September 11, 2012

© 2012 Prokop et al.
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Outline

Text

Alzheimer's disease (AD) pathology displays an inflammatory component characterized by the presence of pro-inflammatory cytokines particularly in response to β-amyloid. Using transgenic APPPS1mice serving as a model of AD, we observed the production of the common interleukin (IL)-12 and IL-23 subunit p40 by microglia. Genetic ablation of p40 and two other IL-12/IL-23 subunits, namely p35 and p19, resulted in a drastic decrease in cerebral amyloid plaque load. Although deletion of IL-12/IL-23 signaling from the radiation-resistant glial compartment of the brain either by removing p40 or its respective receptors was most efficient in mitigating cerebral amyloidosis, peripheral administration of a neutralizing anti-p40 antibody likewise resulted in a significant reduction of cerebral β-amyloid in APPPS1mice. Furthermore intracerebroventricular delivery of anti-p40 antibodies ameliorated behavioral deficits in old APPPS1mice. Our results suggest that inhibition of IL-12/IL-23 signaling reduces cerebral amyloidosis and cognitive dysfunction and poses a novel potential pharmacological target to combat AD.