Experimental Neuroimmunology
Dr. Jonas Neher
Group Leader
Otfried-Müller-Str. 23
72076 Tübingen

jonas.neher@dzne.de
 +49 7071 925-4351

Areas of investigation/research focus

An immune response is part of most neurological diseases, and the development of late-onset Alzheimer's Disease (AD) has been linked to immune related genes and most recently also to epigenetic modifications. This indicates a significant contribution of immunity to AD pathology.

The immune response during AD is largely mediated by the brain's resident macrophages, the microglia, which are attracted to and surround Aβ deposits in the AD brain. However, various aspects of the microglial role in amyloid plaque homeostasis and AD pathogenesis remain unclear. Furthermore, how inflammation in the periphery may affect the immune response in the brain remains incompletely understood.

 more Infos

The main objectives of the group for Experimental Neuroimmunology are:

  1. To understand how microglia contribute to AD pathology and in particular to Aβ plaque formation and Aβ clearance.
  2. To investigate how peripheral inflammatory stimuli alter central immunity, and how this may affect the pathogenesis of AD as well as other neurodegenerative diseases and stroke.

To this end we analyse Aβ precursor protein- (APP) transgenic mouse lines that are 1) deficient in a variety of immune-related molecules, 2) that allow the temporary ablation of microglia, or 3) receive peripheral immune stimulation. We isolate microglia from adult and aged brains and perform gene expression and epigenetic analyses or study their phagocytic behaviour and inflammatory responses in culture.

Our objective is to understand how the brain’s immune system contributes to the pathogenic mechanism of Alzheimer’s disease and to develop therapeutic interventions that target the immune system.

Key Publications

Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani, Michael Gertig, Thomas Ulas, Gaurav Jain, Jessica Wagner, Lisa M. Häsler, Katleen Wild, Angelos Skodras, Thomas Blank, Ori Staszewski, Moumita Datta, Tonatiuh Pena Centeno, Vincenzo Capece, Md. Rezaul Islam, Cemil Kerimoglu, Matthias Staufenbiel, Joachim L. Schultze, Marc Beyer, Marco Prinz, Mathias Jucker, André Fischer & Jonas J. Neher. Innate immune memory in the brain shapes neurological disease hallmarks. Nature, advanced online publication. 2018 Apr 11; 556:332-338. doi: 10.1038/s41586-018-0023-4
Nicholas H. Varvel, Stefan A. Grathwohl, Karoline Degenhardt, Claudia Resch, Andrea Bosch, Mathias Jucker, Jonas J. Neher. Replacement of brain-resident myeloid cells does not alter cerebral amyloid-β deposition in mouse models of Alzheimer's disease. Journal of Experimental Medicine. 2014 Dec 31; 212:1803-1809. doi: 10.1084/jem.20150478
Guy C. Brown, Jonas J. Neher. Microglial phagocytosis of live neurons. Nature Reviews Neuroscience. 2014 Mar 31; 15:209-216. doi: 10.1038/nrn3710
Neher JJ, Emmrich JV, Fricker M, Mander PK, Théry C, Brown GC. Phagocytosis executes delayed neuronal death after focal brain ischemia. Proc Natl Acad Sci U S A. 2013 Oct 22; 110:E4098-107. doi: 10.1073/pnas.1308679110
Neher JJ, Neniskyte U, Zhao JW, Bal-Price A, Tolkovsky AM, Brown GC. Inhibition of microglial phagocytosis is sufficient to prevent inflammatory neuronal death. J Immunol. 2011 Apr 15; 186:4973-83. doi: 10.4049/jimmunol.1003600

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