A high plasma concentration of TNF-alpha is associated with dementia in centenarians

Background Inflammatory mechanisms and immune activation have been hypothes ized to play a role in the pathogenesis of age-associated diseases such as dementia and atherosclerosis. The purpose of this study was to evaluate the plasma concentration of tumor necrosis factor (TNF)-alpha in a large cohor t of centenarians and to look for its possible associations with cognitive function, atherosclerosis, and general health status. Furthermore, we inves tigated whether the concentration of TNF-alpha was correlated with the bloo d concentration of leucocyte subsets or the plasma concentrations of interl eukin (IL)-6, soluble TNF receptor II (sTNFR-II) (75 kDa) and C-reactive pr otein (CRP). Methods. Plasma TNF-alpha was measured by ELISA in 126 centenarians, 45 sub jects aged 81 years, 23 subjects aged 55-65 years, and 38 subjects aged 18- 30 years. Atherosclerosis was evaluated by the ankle-brachial blood pressur e index, and general health status was evaluated by the body mass index and the number of diagnoses present Results. The concentration of TNF-alpha was significantly increased in 126 centenarians compared to younger control groups, and a high concentration o f TNF-alpha was associated with both Alzheimer's disease and generalized at herosclerosis in the centenarians. The concentration of TNF-alpha was posit ively correlated with the concentrations of plasma IL-6, sTNFR-II, and CRP. No associations were found with increased leucocyte subsets or the body ma ss index. Conclusion. This study demonstrates that, even in apparently healthy subjec ts, age-associated immune activation indicated by raised levels of pro-infl ammatory cytokines may reflect age-associated pathological processes that d evelop over decades.