gms | German Medical Science

57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

12. - 15.09.2012, Erlangen

Banner: 57. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie

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

Veröffentlicht: 11. September 2012

© 2012 Prokop et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

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.