Serum BDNF, TNF-α and IL-1β levels in dementia patients

Comparison between Alzheimer’s disease and vascular dementia
  • Chie Yasutake
  • Kenji Kuroda
  • Toshio Yanagawa
  • Takehiko Okamura
  • Hiroshi Yoneda
ORIGINAL PAPER

Abstract

Neurotrophins such as the brain-derived neurotrophic factor (BDNF) are reportedly related to the pathogenesis of Alzheimer’s disease (AD). Several studies have revealed an alteration in BDNF expression in the postmortem brains of AD patients. BDNF has great potential as a therapeutic agent because of its ability to cross the blood–brain barrier and due to its wide in vivo distribution. However, little is known about in vivo BDNF in dementia patients. Moreover, the immunological function of neurotrophins such as BDNF has received great interest. Therefore, we investigated the serum levels of BDNF and cytokines such as TNF-α and IL-1β in dementia patients by the enzyme-linked immunosorbent assay (ELISA). The following subjects were included in this study: 60 AD patients, 60 vascular dementia (VaD) patients and 33 healthy controls. AD and VaD patients were matched for age, gender and severity of dementia. Serum BDNF levels in AD patients were significantly lower than those in VaD patients and controls. TNF-α and IL-1β levels showed no significant difference among the three groups. In the dementia groups, neither the TNF-α nor the IL-1β levels correlated with the BDNF levels. Our results suggest that BDNF may play a pathological role in some cases of AD.

Keywords

Alzheimer’s disease vascular demen- tia BDNF TNF-α IL-1β 

References

  1. 1.
    Whitehouse P, Price D, Stuble R, Clarke A, Delong M (1982) Alzheimer’s disease and senile dementia; loss of neurones in the basal forebrain. Science 215:1237–1239PubMedCrossRefGoogle Scholar
  2. 2.
    Coyle JT, Price DL, Delong MR (1983) Alzheimer’s disease: a disorder of cortical cholinergic innervation. Science 219:1184–1190PubMedCrossRefGoogle Scholar
  3. 3.
    Alderson RF, ALterman AL, Barde YA, Lindsay RM (1990) Brain derived neurotrophic factor increases survival and defferented functions of rat septal cholinergic neurons in culture. Neuron 5:297–306PubMedCrossRefGoogle Scholar
  4. 4.
    Rylett RJ, Williams LR (1994) Role of neurotrophins in cholinergic neurone function in the adult and aged CNS. Trends Neurosci 17:486–490PubMedCrossRefGoogle Scholar
  5. 5.
    Pan W, Banks WA, Fasold MB, Bluth J, Kastin AJ (1998) Transport of brain-derived neurotrophic factor across the blood–brain barrier. Neuropharmacology 37:1553–1561PubMedCrossRefGoogle Scholar
  6. 6.
    Holsinger RM, Schnarr J, Henry P, Castelo VT, Fahnestock M (2000) Quantitation of BDNF mRNA in human parietal cortex by competitive reverse transcription-polymerase chain reaction: decreased levels in Alzheimer’s disease. Brain Res Mol Brain Res 76:347–354PubMedCrossRefGoogle Scholar
  7. 7.
    Connor B, Young D, Yan Q, Faull RL, Synek B, Dragunow M (1997) Brain-derived neurotrophic factor is reduced in Alzheimer’s disease. Brain Res Mol Brain Res 49:71–81PubMedCrossRefGoogle Scholar
  8. 8.
    Phillips HS, Hains JM, Armanini M, Laramee GR, Johnson SA, Winslow JW (1991) BDNF mRNA is decreased in the hippocampus of individuals with Alzheimer’s disease. Neuron 7:695–702PubMedCrossRefGoogle Scholar
  9. 9.
    Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734PubMedGoogle Scholar
  10. 10.
    Donovan MJ, Miranda RC, Kraemer R, McCafferey TA, Tseearollo L, Mahadeo D (1995) Neurotrophin and neurotrophin receptors in vascular smooth muscle cells. Regul Exp Res Inj 147:309–324Google Scholar
  11. 11.
    Nakahashi T, Fujimura H, Altar CA, Li J, Kambayashi J, Tandon NN (2000) Vascular endothelial cells synthesize and secret brain-derived neurotrophic factor. FEBS Lett 470:113–117PubMedCrossRefGoogle Scholar
  12. 12.
    Karege F, Schwald M, Cisse M (2002) Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci Lett 328:261–264PubMedCrossRefGoogle Scholar
  13. 13.
    Ferrer I, Marin C, Rey MJ (1999) BDNF and full-length and truncated TrkB expression in Alzheimer disease. Implications in therapeutic strategies. J Neuropathol Exp Neurol 58:729–739PubMedCrossRefGoogle Scholar
  14. 14.
    Mufson EJ, Kroin JS, Sender TJ, Sobreviela T (1999) Distribution and retrograde transport of trophic factors in the central nervous system: functional implications for the treatment of neurodegenerative disease. Prog Neurobiol 57:451–484PubMedCrossRefGoogle Scholar
  15. 15.
    Miyake K, Yamamoto W, Tadokoro M (2002) Alterations in hippocampal GAP-43, BDNF, and L1 following sustained cerebral ischemia. Brain Res 935:24–31PubMedCrossRefGoogle Scholar
  16. 16.
    Kokaia Z, Nawa H, Uchino H (1996) Regional brain-derived neurotrophic factor mRNA and protein levels following transient forebrain ischemia in the rat. Brain Res Mol Brain Res 38:139–144PubMedCrossRefGoogle Scholar
  17. 17.
    Lindvall O, Ernfors P, Bengzon J (1992) Differential regulation of mRNAs for nerve growth factor, brain-derived neurotrophic factor, and neurotrophin 3 in the adult rat brain following cerebral ischemia and hypoglycemic coma. Proc Natl Acad Sci USA 89:648–652PubMedCrossRefGoogle Scholar
  18. 18.
    Lee J, Fukumoto H, Orne J, Klucken J, Raju S, Vanderburg CR, Irizarry MC, Hyman BT, Ingelsson M (2005) Decreased levels of BDNF protein in Alzheimer temporal cortex are independent of BDNF polymorphisms. Exp Neurol 194:91–96PubMedCrossRefGoogle Scholar
  19. 19.
    Tarkowski E, Blennow K, Wallin A, Tarkowski A (1999) Intracerebral production of tumor necrosis factor-alpha, a local neuroprotective agent, in Alzheimer disease and vascular dementia. J Clin Immunol 19:223–230PubMedCrossRefGoogle Scholar
  20. 20.
    Alvarez XA, Franco A, Fernandez NL, Cacabelos R (1996) Blood levels of histamine, IL-1 beta, and TNF-alpha in patients with mild to moderate Alzheimer disease. Mol Chem Neuropathol 29:237–252PubMedCrossRefGoogle Scholar
  21. 21.
    Toyooka K, Asama K, Watanabe Y (2002) Decreased levels of brain-derived neurotrophic factor in serum of chronic schizophrenic patients. Psychiatry Res 110:249–257PubMedCrossRefGoogle Scholar
  22. 22.
    Gobbo OL, O’Mara SM (2004) Post-tretment,but not pre-treatment, with the selective cyclooxygenase-2inhibitor celecoxob markedly enhances functional recovery from kainic acid-induced neurodegeneration. Neuroscience 125:317–327PubMedCrossRefGoogle Scholar
  23. 23.
    Shimizu E, Hashimoto K, Okamura K, Koike K, Komatsu N, Kumakiri C, Nakazoto M, Watanabe H, Shinoda N, Okada K, Iyo M (2003) Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants. Biol Psychiatry 54:70–75PubMedCrossRefGoogle Scholar
  24. 24.
    Heun R, Kolsch H, Jessen F (2005) Risk factors and early signs of Alzheimer’s disease in a family study sample risk of AD. Eur Arch Psychiatry Clin Neurosci 20Google Scholar
  25. 25.
    Hampel H, Halinger A, Scheloske M, Pedberg F, Fischer P, Unger J, Teipel SJ, Neumann M, Roseenberg C, Osida R, Hulette C, Pongratz D, Ewers M, Kretzschmar HA, Moller HJ (2005) Pattern of interleukin-6 receptor complex immunoreactivity between cortical regions of rapid autopsy normal and Alzheimer’s disease brain. Eur Arch Psychiatry Clin Neurosci 255:269–278PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2006

Authors and Affiliations

  • Chie Yasutake
    • 1
  • Kenji Kuroda
    • 2
  • Toshio Yanagawa
    • 3
  • Takehiko Okamura
    • 3
  • Hiroshi Yoneda
    • 1
  1. 1.Department of NeuropsychiatryOsaka Medical CollegeTakatsukiJapan
  2. 2.Hannan HospitalSakaiJapan
  3. 3.Shinabuyama HospitalTakatsukiJapan

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