A High Plasma Concentration of TNF- Is Associated With Dementia in Centenarians

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Abstract
Background. Inflammatory mechanisms and immune activation have been hypothesized 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)-α in a large cohort of centenarians and to look for its possible associations with cognitive function, atherosclerosis, and general health status. Furthermore, we investigated whether the concentration of TNF-α was correlated with the blood concentration of leucocyte subsets or the plasma concentrations of interleukin (IL)-6, soluble TNF receptor II (sTNFR-II) (75 kDa) and C-reactive protein (CRP). Methods. Plasma TNF-α was measured by ELISA in 126 centenarians, 45 subjects aged 81 years, 23 subjects aged 55–65 years, and 38 subjects aged 18–30 years. Atherosclerosis was evaluated by the ankle-brachial blood pressure index, and general health status was evaluated by the body mass index and the number of diagnoses present. Results. The concentration of TNF-α was significantly increased in 126 centenarians compared to younger control groups, and a high concentration of TNF-α was associated with both Alzheimer's disease and generalized atherosclerosis in the centenarians. The concentration of TNF-α was positively correlated with the concentrations of plasma IL-6, sTNFR-II, and CRP. No associations were found with increased leucocyte subsets or the body mass index. Conclusion. This study demonstrates that, even in apparently healthy subjects, age-associated immune activation indicated by raised levels of pro-inflammatory cytokines may reflect age-associated pathological processes that develop over decades.