Dissecting mechanisms of immune actions in Alzheimer's disease (A06)

• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: from 2008 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 29837756

The project aims to identify the molecular mechanism and cellular players of interleukin (IL)-12/23 mediated changes in Alzheimer's disease (AD) pathology, since in the previous funding period this group identified microglia-produced IL-12/23 as the pathogenetically most relevant immune molecule in an Aß-depositing mouse model of AD. Based on preliminary data indicating that astrocytes are crucial IL-12/23-"downstream target cells", this project will generate and employ Aß-depositing AD mice that lack IL-12 or IL-23 signaling specifically in astrocytes. Moreover, this group will assess, whether IL-12/23 signaling also affects tau pathology in respective AD mouse models. To test the translational potential of existing drugs, they will also repurpose an available small molecule inhibitor of IL-12/23 signaling as well as an existing drug that efficiently and specifically targets the inflammasome component NALP3, whose genetic deficiency in AD mice recently has been shown to substantially alter AD pathology. Another line of investigation will be devoted to testing the role of CD36 in AD pathogenesis in vivo, which acts upstream of NALP3.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 43: The Brain as a Target of Inflammatory Processes
• Major Instrumentation: Stereo Investigator System with motorized focus, brightfield and fluorescence
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)
• Applicant Institution: shared FU Berlin and HU Berlin through:; Charité - Universitätsmedizin Berlin
• Project Head: Professor Dr. Frank Heppner