Project Details
Projekt
T cells as modulators of microglial reactivity in Alzheimer’s disease
Subject Area
Experimental Models for the Understanding of Nervous System Diseases
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular and Cellular Neurology and Neuropathology
Molecular Biology and Physiology of Neurons and Glial Cells
Molecular and Cellular Neurology and Neuropathology
Term
since 2022
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 500118375
Alzheimer´s disease (AD) is the most prevalent neurodegenerative disorder and is pathologically defined by extracellular Aβ deposition, neurofibrillary tangles and neuroinflammation. Microglia are a key component in the pathophysiology of AD and can modulate the disease progression. Enhancing microglial clearance of Aβ by immunotherapy is currently explored in clinical trials with AD patients. In contrast to the microglia-mediated innate immune responses, the contribution of adaptive immunity to the pathophysiology of AD is less investigated. However, we have observed in our preliminary experiments that diverse adaptive immune cell subpopulations invade the AD brain; moreover, we showed in other disease models that brain-invading T cells can modulate the microglial phenotype. Therefore, the objective of this proposal is to investigate the impact of T cell subpopulations on microglial phenotypes and its underlying neuroimmunological mechanisms in AD. We will utilize a combination of ex vivo T cell assays, in vivo cell transplantation, genetic animal models and transcriptomics to study the detailed mechanisms of T cell-microglia interaction. Key findings from animal models in both sexes will then be validated in human brain samples obtained from AD patients. Results derived from this research project will increase our mechanistic understanding of microglia-T cell crosstalk and thereby facilitate the future design of more safe and novel immunotherapeutic approaches for the treatment of AD.
DFG Programme
Priority Programmes
