CD4 and Alzheimer disease: Microbe-derived metabolites are additional contributors to systemic inflammation; for example, alterations of gut microbiota could lead to elevation of phenylalanine and isoleucine concentrations in the periphery of AD mice, which could provoke the infiltration of various immune cells, including T cells, B cells, natural killer cells, neutrophils, dendritic cells, and monocytes; CD4+ T helper (Th)1 cell levels were significantly correlated with M1 microglial activation in the brain during the progression of AD [114].