Chronic stress manifests as depressive- and anxiety-like behavior while recurrent stress elicits disproportionate psychiatric responses linked to stress-induced immunological priming. Based on this evidence, we explored causative mechanisms of how dietary polyphenolics influence Regulatory T Cells and explored their role in preventing mood disorder and Alzheimer’s disease (AD) type cognitive deterioration and neuropathology. Using a conditional Treg depletion transgenic mouse model (Foxp3 cKO), we investigated the cause-effect relationship of Treg expression in mood disorder and AD phenotype preclinically. Interestingly depression and anxiety-like behavior coincide with cognitive decline and AD-type Aβ burden in Foxp3 cKO/5xTg-AD mice by transient depletion of FoxP3. Our studies tentatively support strategies to attenuate Treg immune responses as a potential preventative strategy in attenuating AD-type phenotype.