A blunted T_H17 cytokine signature in women with mild cognitive impairment: insights from inflammatory profiling of a community-based cohort of older adults

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of T_H17 cytokines compared with cells from cognitively healthy women, while myeloid-targeted stimuli elicited similar amounts of cytokines from cells of both groups. This T_H17 signature correlated with the proportion of circulating CD4+ and CD8+ T cells and plasma glial fibrillary acidic protein and neurofilament light concentrations. These results suggest that decreases in T_H17 cytokines could be an early systemic change in women at risk for developing dementia. Amelioration of T_H17s cytokines in early cognitive impairment could, in part, explain the compromised ability of older adults to respond to vaccines or defend against infection.