Emerging evidence delineates critical immune interactions within the gut-brain axis relevant to Alzheimer’s disease (AD). Research from the Buck Institute using 5XFAD mouse models reveals migration of colonic immune cells, particularly CXCR4-positive B cells producing IgA, into the brain, potentially contributing to AD pathology. Dietary interventions rich in fiber demonstrated mitigation of these immune alterations and reduced neurodegenerative frailty. This work offers promising avenues for gut-targeted therapies in neurodegenerative disorders.