Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an increasing prevalence. Despite extensive research, fundamental questions regarding its origins persist. Recent insights have underscored the crucial role of peripheral and central inflammation, challenging the long-held notion of the brain's immune privilege. It is now evident that immune cells play an important role in both healthy and diseased brains. Hence, my project endeavors to contribute to a better understanding of the brain immune landscape in AD, aiming to strategically develop immune-modulatory therapies. Preliminary single-cell sequencing analysis on the immune compartment in the brain of App(NL-G-F) mice subjected to mild peripheral inflammation has revealed a notable reduction of microglial resilience compared to wild type mice, next to an increase in specific T cell populations. In my project, I aim to modulate these microglia and/or T cells in AD setting. I will delve into the intrinsic alterations within microglia to pinpoint targetable pathways that can directly affect the microglial status. Furthermore, I will explore the influence of specific T cell subsets on AD pathology and their potential as therapeutic target. Moreover, I will investigate the skull bone marrow as a source of T cells to the brain. Altogether, by investigating the brain immune landscape in AD pathology, my project aims to identify novel therapeutic targets that complement existing treatments for AD patients.