Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 54, Issue 7 M357-M364, Copyright © 1999 by The Gerontological Society of America

JOURNAL ARTICLE

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

H Bruunsgaard, K Andersen-Ranberg, B Jeune, AN Pedersen, P Skinhoj and BK Pedersen
Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark. infdishb@rh.dk

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)-alpha 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-alpha was correlated with the blood concentration of leucocyte subsets or the plasma concentrations of interleukin (IL)- 6, soluble TNF receptor 11 (sTNFR-H) (75 kDa) and C-reactive protein (CRP). METHODS: Plasma TNF-alpha 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-alpha was significantly increased in 126 centenarians compared to younger control groups, and a high concentration of TNF-alpha was associated with both Alzheimer's disease and generalized atherosclerosis in the centenarians. The concentration of TNF-alpha 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.

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