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Recent research has increasingly focused on the intricate interactions between the brain and the immune system, a critical line of inquiry for understanding neurological disorders like Alzheimer's Disease (AD). AD, once defined primarily by amyloid-β and tau aggregations, is now being explored for its complex interplay with immune processes, offering a deeper understanding of its development. This study delves into the dynamic relationship between the brain and the immune system, utilizing human samples from individuals predisposed to AD and various preclinical models. Our findings reveal that both environmental and genetic risk factors for AD significantly influence immune phenotypes and functions, which in turn impact disease progression. Further, we discovered that disrupting brain-spleen communication alters myeloid cell fate and cognitive performance in 5xFAD mice. These insights demonstrate the profound and reciprocal influence between the brain and the immune system. They underscore the importance of these interactions in understanding not only AD but also a wider array of neurological conditions, suggesting that this interplay is crucial for comprehending the complexities of such diseases. Zoom Link: https://weizmann.zoom.us/j/5420322495?pwd=ZmhUR0kxWTB6aDh0bklBNFlzV1JNdz09 Meeting ID: 542 032 2495 Password: 862769