Neurobiology of Aging
Volume 30, Issue 5 , Pages 769-781 , May 2009

Genetic priming of a proinflammatory profile predicts low IQ in octogenarians

  • K.S. Krabbe

      Affiliations

    • The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
    • Corresponding Author InformationCorresponding author at: Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Tel.: +45 35 45 73 77; fax: +45 35 45 76 44.
    • ,
  • E.L. Mortensen

      Affiliations

    • Institute of Public Health, University of Copenhagen, Denmark
    • Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
    • Present address: Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Øster Farimagsgade 5, opg Z, 1 sal, DK-1014 Copenhagen, Denmark.
    • ,
  • K. Avlund

      Affiliations

    • Institute of Public Health, University of Copenhagen, Denmark
    • Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
    • Present address: Institute of Public Health, Faculty of Health Sciences, University of Copenhagen, Øster Farimagsgade 5, Building 9, Post Box 2099, DK-1014 Copenhagen, Denmark.
    • ,
  • H. Pilegaard

      Affiliations

    • The August Krogh Building, Institute of Molecular Biology, University of Copenhagen, Denmark
    • Present address: The August Krogh Building, Room 431, Institute of Molecular Biology, University of Copenhagen, Universitetsparken 13, DK-2100 Copenhagen, Denmark.
    • ,
  • L. Christiansen

      Affiliations

    • Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Denmark
    • Present address: Institute of Public Health, Department of Epidemiology, University of Southern Denmark, J.B. Winsløws Vej 9, DK-5000 Odense C, Denmark.
    • ,
  • A.N. Pedersen

      Affiliations

    • National Food Institute, Technical University of Denmark, Denmark
    • Present address: National Food Institute, Technical University of Denmark, Anker Engelundsvej 1, 101 A, DK-2800 Kgs. Lyngby, Denmark.
    • ,
  • M. Schroll

      Affiliations

    • Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
    • Present address: Research Centre for Prevention and Health, Building 84/85, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
    • ,
  • T. Jørgensen

      Affiliations

    • Research Centre for Prevention and Health, Glostrup University Hospital, Glostrup, Denmark
    • Present address: Research Centre for Prevention and Health, Building 84/85, Glostrup University Hospital, DK-2600 Glostrup, Denmark.
    • ,
  • B.K. Pedersen

      Affiliations

    • The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
    • Present address: Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
    • ,
  • H. Bruunsgaard

      Affiliations

    • The Centre of Inflammation and Metabolism, Department of Infectious Diseases and CMRC, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark
    • Present address: Centre of Inflammation and Metabolism, Rigshospitalet, Section 7641, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.

Received 8 May 2007 ,Revised 11 July 2007 ,Accepted 21 August 2007.

References 

  1. Alvarez A, Cacabelos R, Sanpedro C, Garcia-Fantini M, Aleixandre M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-I in Alzheimer disease. Neurobiol. Aging. 2006;28:533–536
  2. Alvarez V, Mata IF, Gonzalez P, Lahoz CH, Martinez C, Pena J, et al. Association between the TNFalpha-308 A/G polymorphism and the onset-age of Alzheimer disease. Am. J. Med. Genet. 2002;114:574–577
  3. Avlund K, Kreiner S, Schultz-Larsen K. Functional ability scales for the elderly. A validation study. Eur. J. Public Health. 1996;6:35–42
  4. Bauer J, Strauss S, Schreiter-Gasser U, Ganter U, Schlegel P, Witt I, et al. Interleukin-6 and alpha-2-macroglobulin indicate an acute-phase state in Alzheimer's disease cortices. FEBS Lett. 1991;285:111–114
  5. Biessels GJ, Staekenborg S, Brunner E, Brayne C, Scheltens P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol. 2006;5:64–74
  6. Bruunsgaard H. Physical activity and modulation of systemic low-level inflammation. J. Leukoc. Biol. 2005;78:819–835
  7. Bruunsgaard H, Andersen-Ranberg K, Hjelmborg JB, Pedersen BK, Jeune B. Elevated levels of tumor necrosis factor alpha and mortality in centenarians. Am. J. Med. 2003;115:278–283
  8. Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK. A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J. Gerontol. A Biol. Sci. Med. Sci. 1999;54:M357–M364
  9. Bruunsgaard H, Benfield T, Andersen-Ranberg K. The TNF-308G>A polymorphism is associated with dementia in the oldest old. J. Am. Geriatr. Soc. 2004;52:1361–1366
  10. Bruunsgaard H, Christiansen L, Pedersen AN, Schroll M, Jørgensen T, Pedersen BK. The IL6-174 G>C polymorphism is associated with cardiovascular diseases and mortality in 80-year-old humans. Exp. Gerontol. 2004;39:255–261
  11. Bruunsgaard H, Pedersen BK. Age-related inflammatory cytokines and disease. Immunol. Allergy Clin. North Am. 2003;23:15–39
  12. Bruunsgaard H, Pedersen M, Pedersen BK. Aging and proinflammatory cytokines. Curr. Opin. Hematol. 2001;8:131–136
  13. Christiansen L, Bathum L, Andersen-Ranberg K, Jeune B, Christensen K. Modest implication of interleukin-6 promoter polymorphisms in longevity. Mech. Ageing Dev. 2004;125:391–395
  14. Culpan D, MacGowan SH, Ford JM, Nicoll JA, Griffin WS, Dewar D, et al. Tumour necrosis factor-alpha gene polymorphisms and Alzheimer's disease. Neurosci. Lett. 2003;350:61–65
  15. Dandona P, Aljada A, Bandyopadhyay A. Inflammation: the link between insulin resistance, obesity and diabetes. Trends Immunol. 2004;25:4–7
  16. Depboylu C, Du Y, Muller U, Kurz A, Zimmer R, Riemenschneider M, et al. Lack of association of interleukin-10 promoter region polymorphisms with Alzheimer's disease. Neurosci. Lett. 2003;342:132–134
  17. Dik MG, Jonker C, Hack CE, Smit JH, Comijs HC, Eikelenboom P. Serum inflammatory proteins and cognitive decline in older persons. Neurology. 2005;64:1371–1377
  18. Engelhart MJ, Geerlings MI, Meijer J, Kiliaan A, Ruitenberg A, van Swieten JC, et al. Inflammatory proteins in plasma and the risk of dementia: the rotterdam study. Arch. Neurol. 2004;61:668–672
  19. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), 2001. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP). JAMA 285, 2486–2497.
  20. Felderhoff-Mueser U, Schmidt OI, Oberholzer A, Buhrer C, Stahel PF. IL-18: a key player in neuroinflammation and neurodegeneration?. Trends Neurosci. 2005;28:487–493
  21. Gale CR, Martyn CN, Cooper C. Cognitive impairment and mortality in a cohort of elderly people. BMJ. 1996;312:608–611
  22. Giedraitis V, He B, Huang WX, Hillert J. Cloning and mutation analysis of the human IL-18 promoter: a possible role of polymorphisms in expression regulation. J. Neuroimmunol. 2001;112:146–152
  23. Griffin WS, Stanley LC, Ling C, White L, MacLeod V, Perrot LJ, et al. Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease. Proc. Natl. Acad. Sci. U.S.A. 1989;86:7611–7615
  24. Hagerup L, Hansen PF. [An investigation of 50-year-old persons in Glostrup in 1964–1965]. Ugeskr. Laeger. 1968;130:1145–1148
  25. Huth C, Heid IM, Vollmert C, Gieger C, Grallert H, Wolford JK, et al. IL6 gene promoter polymorphisms and type 2 diabetes: joint analysis of individual participants’ data from 21 studies. Diabetes. 2006;55:2915–2921
  26. Krabbe KS, Pedersen M, Bruunsgaard H. Inflammatory mediators in the elderly. Exp. Gerontol. 2004;39:687–699
  27. Kroeger KM, Carville KS, Abraham LJ. The -308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol. Immunol. 1997;34:391–399
  28. Kurreeman FA, Schonkeren JJ, Heijmans BT, Toes RE, Huizinga TW. Transcription of the IL10 gene reveals allele-specific regulation at the mRNA level. Hum. Mol. Genet. 2004;13:1755–1762
  29. In:  Larsen L editors. Gerontopsykologi. Århus Universitetsforlag; 2007;
  30. Laws SM, Perneczky R, Wagenpfeil S, Muller U, Forstl H, Martins RN, et al. TNF polymorphisms in Alzheimer disease and functional implications on CSF beta-amyloid levels. Hum. Mutat. 2005;26:29–35
  31. Licastro F, Pedrini S, Caputo L, Annoni G, Davis LJ, Ferri C, et al. Increased plasma levels of interleukin-1, interleukin-6 and alpha-1-antichymotrypsin in patients with Alzheimer's disease: peripheral inflammation or signals from the brain?. J. Neuroimmunol. 2000;103:97–102
  32. Lindberg C, Chromek M, Ahrengart L, Brauner A, Schultzberg M, Garlind A. Soluble interleukin-1 receptor type II, IL-18 and caspase-1 in mild cognitive impairment and severe Alzheimer's disease. Neurochem. Int. 2005;46:551–557
  33. Lio D, Annoni G, Licastro F, Crivello A, Forte GI, Scola L, et al. Tumor necrosis factor-alpha-308A/G polymorphism is associated with age at onset of Alzheimer's disease. Mech. Ageing Dev. 2006;127:567–571
  34. Lowe PR, Galley HF, Abdel-Fattah A, Webster NR. Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. Crit. Care Med. 2003;31:34–38
  35. Lucas SM, Rothwell NJ, Gibson RM. The role of inflammation in CNS injury and disease. Br. J. Pharmacol. 2006;147(Suppl. 1):S232–S240
  36. Morganti-Kossmann MC, Rancan M, Stahel PF, Kossmann T. Inflammatory response in acute traumatic brain injury: a double-edged sword. Curr. Opin. Crit. Care. 2002;8:101–105
  37. Mortensen EL, Hogh P. A gender difference in the association between APOE genotype and age-related cognitive decline. Neurology. 2001;57:89–95
  38. Mortensen EL, Kleven M. A WAIS longitudinal study of cognitive development during the life span from ages 50 to 70. Dev. Neuropsychol. 1993;9:115–130
  39. Qi L, van Dam RM, Meigs JB, Manson JE, Hunter D, Hu FB. Genetic variation in IL6 gene and type 2 diabetes: tagging-SNP haplotype analysis in large-scale case–control study and meta-analysis. Hum. Mol. Genet. 2006;15:1914–1920
  40. Ramos EM, Lin MT, Larson EB, Maezawa I, Tseng LH, Edwards KL, et al. Tumor necrosis factor alpha and interleukin 10 promoter region polymorphisms and risk of late-onset Alzheimer disease. Arch. Neurol. 2006;63:1165–1169
  41. Reuss E, Fimmers R, Kruger A, Becker C, Rittner C, Hohler T. Differential regulation of interleukin-10 production by genetic and environmental factors—a twin study. Genes Immun. 2002;3:407–413
  42. Ritchie K, Kildea D. Is senile dementia “age-related” or “ageing-related”?—evidence from meta-analysis of dementia prevalence in the oldest old. Lancet. 1995;346:931–934
  43. Ross R. Atherosclerosis—an inflammatory disease. N. Engl. J. Med. 1999;340:115–126
  44. Schaie KW. The course of adult intellectual development. Am. Psychol. 1994;49:304–313
  45. Schaie KW, Willis SL, Pennak S. An historical framework for cohort differences in intelligence. Res. Hum. Dev. 2005;2:43–67
  46. Schippers EF, van’t Veer C, van Voorden S, Martina CA, Huizinga TW, le Cessie S, et al. IL-10 and toll-like receptor-4 polymorphisms and the in vivo and ex vivo response to endotoxin. Cytokine. 2005;29:215–228
  47. Schroeter M, Jander S. T-cell cytokines in injury-induced neural damage and repair. Neuromol. Med. 2005;7:183–195
  48. Sie MP, Sayed-Tabatabaei FA, Oei HH, Uitterlinden AG, Pols HA, Hofman A, et al. Interleukin 6-174 g/c promoter polymorphism and risk of coronary heart disease: results from the rotterdam study and a meta-analysis. Arterioscler. Thromb. Vasc. Biol. 2007;26:212–217
  49. Tan ZS, Beiser AS, Vasan RS, Roubenoff R, Dinarello CA, Harris TB, et al. Inflammatory markers and the risk of Alzheimer disease: the Framingham Study. Neurology. 2007;68:1902–1908
  50. Tarkowski E, Andreasen N, Tarkowski A, Blennow K. Intrathecal inflammation precedes development of Alzheimer's disease. J. Neurol. Neurosurg. Psychiatry. 2003;74:1200–1205
  51. Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, Blennow K. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res. Bull. 2003;61:255–260
  52. Tracey KJ. The inflammatory reflex. Nature. 2002;420:853–859
  53. van Oijen M, Arp PP, Jong FJ, Hofman A, Koudstaal PJ, Uitterlinden AG, et al. Polymorphisms in the interleukin 6 and transforming growth factor beta1 gene and risk of dementia The Rotterdam Study. Neurosci. Lett. 2006;402:113–117
  54. Weaver JD, Huang MH, Albert M, Harris T, Rowe JW, Seeman TE. Interleukin-6 and risk of cognitive decline: MacArthur studies of successful aging. Neurology. 2002;59:371–378
  55. Wechsler D. The Measurement and Appraisal of Adult Intelligence. Williams & Wilkins; 1958;
  56. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc. Natl. Acad. Sci. U.S.A. 1997;94:3195–3199
  57. Wright CB, Sacco RL, Rundek TR, Delman JB, Rabbani LE, Elkind MS. Interleukin-6 is associated with cognitive function: the Northern Manhattan Study. J. Stroke Cerebrovasc. Dis. 2006;15:34–38
  58. Wyss-Coray T. Inflammation in Alzheimer disease: driving force, bystander or beneficial response?. Nat. Med. 2006;12:1005–1015
  59. Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, et al. The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA. 2004;292:2237–2242
  60. Yaffe K, Lindquist K, Penninx BW, Simonsick EM, Pahor M, Kritchevsky S, et al. Inflammatory markers and cognition in well-functioning African-American and white elders. Neurology. 2003;61:76–80
  61. Yucesoy B, Peila R, White LR, Wu KM, Johnson VJ, Kashon ML, et al. Association of interleukin-1 gene polymorphisms with dementia in a community-based sample: the Honolulu-Asia Aging Study. Neurobiol. Aging. 2006;27:211–217

PII: S0197-4580(07)00347-8

doi: 10.1016/j.neurobiolaging.2007.08.013

Neurobiology of Aging
Volume 30, Issue 5 , Pages 769-781 , May 2009

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