title: A high plasma concentration of TNF-alpha is associated with dementia in centenarians.
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)-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Denmark. infdishb@rh.dk
authors.forename: H
authors.initials: H
authors.lastname: Bruunsgaard
authors.forename: K
authors.initials: K
authors.lastname: Andersen-Ranberg
authors.forename: B
authors.initials: B
authors.lastname: Jeune
authors.forename: A N
authors.initials: AN
authors.lastname: Pedersen
authors.forename: P
authors.initials: P
authors.lastname: Skinhøj
authors.forename: B K
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood*; D015703:Antigens, CD / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D003071:Cognition; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein