Artikel
Reducing alzheimer´s disease β-amyloid and cognitive deficits by manipulating il-12/il-23 signaling
Suche in Medline nach
Autoren
-
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
| Veröffentlicht: | 11. September 2012 |
|---|
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.
