Innate and adaptive immune basis of mental health effect on Alzheimer's disease progression

Mental health has long been suspected to be highly associated with neurodegenerative disease, but it lacks experimental evidence to elaborate the link and immunological mechanism between them. In this work, we studied the progression of Alzheimers disease (AD) and its associated immune activity by using the transgenic mice under negative (depression) and positive (environmental enrichment, EE) mental health intervention. The tissue pathology, resident and peripheral immunity and behavioral characteristics were investigated. The transgenic mice undergoing depression treatment was featured with aggravated AD pathology, elevated activation of microglia in the brains, more abundance of Treg cells and cytotoxic T cells, and higher ratios of central memory T cells to effector memory T (TCM-to-TEM) cells in the peripheral blood and spleens. The EE treated mice were featured with alleviated AD pathology, reduced activation of microglia, less amounts of Treg and cytotoxic T cells and lower ratios of TCM-to-TEM cells. This study may provide strategies for immunity regulation and mental health intervention that benefit AD therapy. Significance statementMental health is suspected to regulate AD progression, but its validation in histology examination and the regulatory mechanism remains unclear. Here, we prove that both innate and adaptive immunity are playing important roles and mental health-immunity-AD progression forms a triad. More active microglia, Treg, and cytotoxic T cells, and higher TCM-to-TEM feature negative mental health and severer AD progress, and vice versa. The findings in adaptive immunity and the triad may inspire AD regulation.