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.
The main objectives of the group for Experimental Neuroimmunology are:
- To understand how microglia contribute to AD pathology and in particular to Aβ plaque formation and Aβ clearance.
- 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.