DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20160509

Plasma levels of vitamin B12, epidermal growth factor and tumor necrosis factor alpha in patients with alzheimer dementia

Hatice Ferhan Komurcu, Nedret Kilic, Melike Erol Demirbilek, Kadir Okhan Akin

Abstract


Background: It was previously reported that vitamin B12 (Vit B12) has the regulatory effects on epidermal growth factor (EGF) and tumor necrosis factor alpha (TNF-α). The role of Vit B12, EGF and TNF-α in the pathogenesis of alzheimer dementia has not been elucidated yet. In this study the plasma Vit B12, EGF and TNF-α level were examined in individuals, between 65-99 years old with and without alzheimer dementia (AD).  

Methods: The study group comprised 47 patients with AD and 38 cases without dementia. EGF and TNF-α were analyzed by ELISA, and Vit B12 was analyzed by chemiluminescence method.

Results: Vit B12 and EGF levels were significantly lower (p<0.0001), whereas TNF-α levels were significantly higher (p<0.0001) in the AD group in comparison to those without AD.  

Conclusions: Our results suggest that Vit B12, EGF and TNF-α may have a role in the pathophysiology of AD.  


Keywords


Alzheimer dementia, Vitamin B12, Epidermal growth factor, Tumor necrosis factor alpha

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References


Adelman AM, Daly MP. Initial evaluation of the patient with suspected dementia. Am Fam Physician. 2005;71(9):1745-50.

Green A. Biochemical investigation in patients with dementia. Ann Clin Biochem. 2002;39(Pt 3):211-20.

Jorm AF, Korten AE, Henderson AS. The prevalance of dementia: A quatitative integration of the literature. Acta Psychiatr Scand. 1987;76(5):465-79.

Hutto BR. Folate and cobalamin in psychiatric illness. Compr Psychiatry. 1997;38(6):305-14.

Wang H-X, Wahlin A, Basun H, Fastbom J, Winblad B, et al. Vitamin B(12) and folate in relation to the development of Alzheimer disease. Neurology. 2001;56(9):1188-94.

Scalabrino G. Cobalamin (Vitamin B12) in subacute combined degeneration and beyond: traditional interpretations and novel theories. Exp Neurol. 2005;192(2):463-79.

McCaddon A, Regland B, Hudson P, Davies G. Functional Vitamin B12 deficiency and Alzheimer disease. Neurology. 2002;58(9):1395-9.

Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, et al. Folate, vitamine B12 and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55(11):1449-55.

Ikeda T, Furukawa Y, Mashimoto S, Takahashi J, Yamada M. Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer’s disease. Acta Psychiatr Scand. 1990;82(4):327-9.

Eastley R, Wilcock GK, Bucks RS. Vitamin B12 deficiency in dementia and cognitive impairment: the effects on treatment of neuropsychological function. Int J Geriatr Psychiatry. 2000;15(3):226-33.

Miller JW. Vitamin B12 deficiency, tumor necrosis factor-alpha and epidermal growth factor: A novel function for vitamin B12? Nutr Rev. 2002;60(5Pt 1):142-4.

Scalabrino G. Subacute combined degeneration one century later. The Neurotropic action of cobalamin (vitamine B12) revisited. J neuropathol exp neurol. 2001;60(2):109-20.

McGeer PL, McGeer EG. Inflammatıon, autotoxicity and Alzheimer disease. Neurobiol Aging. 2001;22(6):799-809.

Yamada M, Ikeuchi T, Hatanaka H. The neurotrophic action and signalling of epidermal growth factor. Prog Neurobiol. 1997;51(1):19-37.

Perry RT, Collins JS, Wiener H, Acton R, Go RC. The role of TNF and its receptors in Alzheimer’s disease. Neurobiol Aging. 2001;22(6):873-83.

Gruen JR, Weissman SM. Evolving views of the major histocompatibility complex. Blood. 1997;90(11):4252-65.

Makhatadze NJ. Tumor necrosis factor locus: Genetic organization and biological implications. Hum Immunol. 1998;59(9):571-9.

Marino MW, Dunn A, Grail D, Inglese M, Noguchi Y, et al. Characterization of tumor necrosis factor - deficient mice. Proc Natl Acad Sci USA. 1997;94(15):8093-8.

Selmaj KW, Farooq M, Norton WT, Raine JS, Brosnan CF. Proliferation of astrocytes in vitro in response to cytokines. A primary role for tumor necrosis factor. J Immunol. 1990;144(1):129-35.

Benveniste EN, Sparacio SM, Norris JG, Grenett HE, Fuller GM. Induction and regulation of interleukin-6 gene expression in rat astrocytes. J Neuroimmunol. 1990;30(2-3):201-12.

Van snick J. Interleukin-6: An overview. Annu Rev Immunol. 1990;8:253-78.

Allen RH, Stabler SP, Savage DG, Lindenbaum J. Metabolic abnormalities in cobalamin (vitamin B12) and folate deficiency. FASEB J. 1993;7(14):1344-53.

Martin D, Miller G, Fischer N. Neuroprotective strategies based on interleukin signaling. In: Mattson MP, ed. Neuroprotective signal transduction. Totowa, New Jersey: Humana Press. 1998:185-95.

Brauwer M, Chamulitrat W, Ferruzzi G, Sauls DL, Weinberg JB. Nitric oxide interactions with cobalamins: biochemical and functional consequences. Blood. 1996;88(5):1857-64.

Folstein MF, Folstein SE, McHugh PR. Mini-mental state. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189-98.

McKhann G, Drachman D, Folstein M, Katzman R, Price D, et al. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34(7):939-44.

American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders (DSM IV) fourth ed. Washington: American Psychiatric Association.

Bottiglieri T. Folate, Vitamin B12, and neuropsychiatric disorders. Nutr Rev. 1996;54(12):382-90.

Engelborghs S, Vloeberghs E, Maertens K, Mariën P, Somers N, et al. Correlations between cognitive behavioural and psychological findings and levels of vitamin B12 and folate in patients with dementia. International Journal of Geriatric Psychiatry. 2004;19(4):365-70.

Whyte EM, Mulsant BH, Butters MA, Qayyum M, Towers A, et al. Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementia. Am J Geriatr Psychiatry. 2002;10(3):321-7.

Moretti R, Torre P, Antonello RM , Cazzato G, Cattaruzza T, et al. Vitamin B12 and folate depletion: clinical evidence in a neurological population. Neurologist. 2004;10(6):338 -43.

Mizrahi EH, Bowirrat A, Jacobsen DW, Korczyn AD, Traore F, et al. Plasma homocysteine, vitamin B12 and folate in Alzheimer’s patients and healthy Arabs in Israel. J Neurol Sci. 2004;227(1):109-13.

Dominguez RO, Marschoff ER, Guareschi EM, Famulari AL, Pagano MA, et al. Homocysteine, vitamine B12 and folate in Alzheimer’s and vascular dementias: the paradoxical effect of the superimposed type II diabetes mellitus condititon. Clin Chim Acta. 2005;359(1-2):163-70.

Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G, et al. Vitamin B12 and folate depletion in cognition: a review. Neurol India. 2004;52(3):310-8.

Peracchi M, Bomonti Catena F, Pomati M, De Franceschi M, et al. Human cobalamin deficiency: alterations in serum tumor necrosis factor-alpha and epidermal growth factor. Eur J Haematol. 2001;67(2):123-27.

Scalabrino G, Nicolini G, Buccellato FR, Peracchi M, Tredici G, et al. Epidermal growth factor as a local mediator of the neurotrophic action of vitamin B(12) (cobalamin) in the rat central nervous system. FASEB J. 1999;13(14):2083-90.

Scalabrino G, Tredici G, Buccellato FR, Manfridi A. Further evidence for the involvement of epidermal growth factor in the signaling pathway of vitamin B12 (cobalamin) in the rat central nervous system. J Neuropathol Exp Neurol. 2000;59(9):808- 14.

Morganti- Kossmann MC, Kossman T, Wahl SM. Cytokines and neuropathology. Trends Pharmacol Sci. 1992;13(7):286-91.

Tarkowski E, Liljeroth AM, Minthon L, Tarkowski A, Wallin A, et al. Cerebral pattern of pro- and anti-inflammatory cytokines in dementias. Brain Res Bull. 2003;61(3):255-60.