Emerging research elucidates the intricate immunological crosstalk between the gut and brain in Alzheimer’s disease (AD). Studies using the 5XFAD amyloid-β mouse model reveal altered immune cell profiles in colonic tissues, including decreased plasma cells and increased migratory B cell subsets characterized by CXCR4 expression. These cells appear to traffic from the gut to the brain, correlating with heightened inflammatory signals from glial cells. Dietary interventions high in fiber show potential to ameliorate gut immune dysregulation and reduce AD-associated pathology. Such findings illuminate novel pathways within the gut-brain axis, strengthening the rationale for immunomodulatory and microbiome-targeted strategies in neurodegenerative disease therapy.