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Influence of vitamin B12 on brain methionine adenosyltransferase activity in senile dementia of the Alzheimer's type

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Summary

The influence of vitamin B12 on the activity of methionine adenosyltransferase (MAT) in postmortem brains of patients with senile dementia of the Alzheimer's type (SDAT) was investigated. In samples of cortex gyrus frontalis from SDAT patients with normal and low levels of serum B12, MAT Vmax was significantly increased by 25% and 19%, respectively. MAT Vmax from a SDAT group chronically treated with B12 was similar to controls. In contrast to cortex gyrus frontalis, no significant alterations were seen in MAT activity in nucleus caudatus. This study provides evidence that SDAT is associated with significant alterations in transmethylation mechanisms in specific regions of the brain. The relationship between blood levels of B12 and the actual status of this vitamin in the brain influencing the rates of synthesis of both methionine and SAM may, however, be far more complex and cannot be directly clarified on the basis of the present human brain results.

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References

  • American Psychiatric Association (1980) Diagnostic and statistical manual of mental disorders, 3rd edn. APA, Washington, DC

    Google Scholar 

  • Banerjee RV, Matthews RG (1990) Cobalamin-dependent methionine synthetase. FASEB J 4: 1450–1459

    Google Scholar 

  • Blennow K (1990) Heterogeneity of Alzheimer's disease. Thesis, University of Gothenburg

  • Bottiglieri T, Godfrey P, Flynn T, Carney MWP, Toone BK, Reynolds EH (1990) Cerebrospinal fluid S-adenosylmethionine in depression and dementia: effects of treatment with parenteral and oral S-adenosylmethionine. J Neurol Neurosurg Psychiatry 53: 1096–1098

    Google Scholar 

  • Bustany P, Sargent T, Saudubray JH, Henry JF, Comar D (1981) Regional human brain uptake and protein incorporation of L-(11C) methionine studied in vivo by PET. J Cereb Blood Flow Metab [Suppl 1]: S17-S18

    Google Scholar 

  • Cantoni GL, Durell J (1957) Activation of methionine for transmethylation. II. The methionine activating enzyme: studies on the mechanism of the reaction. J Biol Chem 225: 1033–1048

    Google Scholar 

  • Cohen BM, Satlin A, Zubenko GS (1988) S-adenosyl-L-methionine in the treatment of Alzheimer's disease. J Clin Psychopharmacol 8: 43–47

    Google Scholar 

  • De Vasconcelos-Cunha UG, Rocha FL, De Souza-Peixoto JM, De Morao Motta MF, Barbosa MT (1995) Vitamin B12 deficiency and dementia. Int Psychogeriatr 7: 85–88

    Google Scholar 

  • Ellison DW, Beal MF, Mazurek MF, Brid D, Martin JB (1986) A postmortem study of amino acid neurotransmitters in Alzheimer's disease. Ann Neurol 20: 616–621

    Google Scholar 

  • Finkelstein JD, Martin JJ (1986) Methionine metabolism in mammals. J Biol Chem 261: 1582–1587

    Google Scholar 

  • Garras A, Djurhuus R, Christensen B, Lillehaug JR, Ueland PM (1991) A nonradioactive assay for 5N-methyltetrahydrofolate-homocysteine methyltransferase (methionine synthase) based on O-phtaldialdehyde derivatization of methionine and fluorescence detection. Anal Biochem 199: 112–118

    Google Scholar 

  • Gomes-Trolin C, Löfberg C, Trolin G, Oreland L (1994) Brain ATP:L-methionine S-adenosyltransferase (MAT) and S-adenosylhomocysteine (SAH): regional distribution and age-related changes. Eur Neuropsychopharmacol 4: 469–478

    Google Scholar 

  • Gomes-Trolin C, Regland B, Oreland L (1995) Decreased methionine adenosyltransferase activity in erythrocytes of patients with dementia disorders. Eur Neuropsychopharmacol 5: 107–114

    Google Scholar 

  • Grange E, Gharib A, Lepetit P, Guillaud J, Sarda N, Bobiliter P (1992) Brain protein synthesis in the conscious rat using L-[35S] methionine: relationship of methionine specific activity between plasma and precursor compartment and evaluation of methionine metabolic pathways. J Neurochem 59: 1437–1443

    Google Scholar 

  • Greene RC (1969) Kinetic studies of the mechanisms of S-adenosylmethionine synthetase from yeast. Biochem 8: 2255–2265

    Google Scholar 

  • Hardy JA, Wester P, Winblad B, Gezelius C, Bring G, Eriksson A (1985) The patients dying after long terminal phase have acidotic brains; implications for biochemical measurements on autopsy tissues. J Neurotransm 61: 253–264

    Google Scholar 

  • Ikeda T, Furukawa Y, Mashimoto S, Takahashi K, Yamada M (1990) Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer's disease. Acta Psychiatr Scand 82: 327–339

    Google Scholar 

  • Ikeda T, Yamamoto K, Takahashi K, Kaku Y, Uchoyama M, Sugiyama K, Yamada M (1992) Treatment of Alzheimer-type dementia with intravenous mecobalamin. Clin Ther 14: 426–437

    Google Scholar 

  • Inada M, Toyoshima M, Masakuni K (1982) Cobalamin contents of th brains in some clinical and pathologic states. Int J Vit Nutr Res 52: 423–429

    Google Scholar 

  • Jacobsen SJ, Hoffman RM, Erbe RW (1980) Regulation of methionine adenosyl-transferase in normal diploid and simian virus 40-transformed human fibroblasts. J Natl Can Inst 65: 1237–1244

    Google Scholar 

  • Jolles PR, Chapman PR, Alabi A (1989) PET, CT, and MRI in the evaluation of neuropsychiatric disordes: current applications. J Nucl Med 30: 1589–1606

    Google Scholar 

  • Katzman R, Kawas C (1986) The evolution of the diagnosis of dementia: past, present, and future. In: Peock K, Freund HJ, Gänshirt H (eds) Neurology. Springer, Berlin Heidelberg New York Tokyo, pp 43–49

    Google Scholar 

  • Kingsbury AE, Foster OJF, Nisbet AP, Cairns N, Bray L, Eve DJ, Lees AJ, Marsden CD (1995) Tissue pH as an indicator of mRNA preservation in human post-mortem brain. Mol Brain Res 28: 311–318

    Google Scholar 

  • Kotb M, Geller AM (1993) Methionine adenosyltransferase: structure and function. Pharmacol Ther 59: 125–143

    Google Scholar 

  • Levitt AJ, Karlinsky H (1992) Folate, Vitamin B12 and cognitive impairment in patients with Alzheimer's disease. Acta Psychiatr Scand 86: 301–305

    Google Scholar 

  • Mann DMA, Neary D, Yates PO, Lincoln J, Snowden JS, Stanworth P (1981) Alterations in protein synthetic capability of nerve cells in Alzheimer's disease. J Neurol Neurosurg Psychiatry 44: 97–102

    Google Scholar 

  • Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry procedure to simplifly protein determination in membrane and lipoprotein samples. Anal Biochem 87: 206–210

    Google Scholar 

  • Martin DC, Francis J, Protetch J, Huff FJ (1992) Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 40: 168–172

    Google Scholar 

  • McCaddon A, Kelly CL (1994) Familial Alzheimer's disease and vitamin B12 deficiency. Age Ageing 23: 334–337

    Google Scholar 

  • McKeever MP, Weir DG, Molloy A, Scott JM (1991) Betaine-homocysteine methyl-transferase: organ distribution in man, pig and rat and subcellular distribution in the rat. Clin Sci 81: 551–556

    Google Scholar 

  • McKeever M, Molloy A, Young P, Kennedy S, Kennedy DG, Scott JM (1995) Demonstration of hypomethylation of proteins in the brain of pigs (but not rats) associated with chronic vitamin B12 inactivation. Clin Sci 88: 471–477

    Google Scholar 

  • McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) 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. Neurol 34: 939–944

    Google Scholar 

  • Meadows ME, Kaplan RF, Bromfield EB (1994) Cognitive recovery with vitamin B12 therapy: a longitudinal neuropsychological assessment. Neurology 44: 1764–1765

    Google Scholar 

  • Mitsuyama Y, Kogoh H (988) Serum and cerebrospinal fluid vitamin B12 levels in demented patients with CH3-B12 treatment. Preliminary study. Jpn J Psychiatry Neurol 42: 65–71

    Google Scholar 

  • Morrison LD, Kish SJ (1995) Brain polyamine levels are altered in Alzheimer's disease. Neurosci Lett 197: 5–8

    Google Scholar 

  • Mudd SH, Cantoni GL (1964) Biological transmethylation, methyl-groups neogenesis and other ‘one-carbon’ metabolic reactions dependent upon tetrahydrofolic acid. In: Florkin M, Stotz H (eds) Comprehensive biochemistry. Elsevier, Amsterdam, pp 1–47

    Google Scholar 

  • Ordonez LA (1977) Control of the availability to the brain of folic acid, vitamin B12 and choline. In: Wurtman RJ, Wurtman JJ (eds) Nutrition and the brain. Raven Press, New York, pp 205–248

    Google Scholar 

  • Oreland L, Hiraga Y, Jossan SS, Regland B, Gottfries CG (1990) Increased monoamine oxidase activity and vitamin B12 deficiency in dementia disorders. In: Dostert P, Riederer P, Strolin Benedetti M, Roncucci R (eds) Early markers in Parkinson's and Alzheimer's diseases. Springer, Wien New York, pp 267–286 (New Vistas in Drug Research, vol 1)

    Google Scholar 

  • Perry EK, Gibson PH, Blessed G, Perry RH, Tomlinson BE (1977) Neurotransmitter enzyme abnormalities in senile dementia. J Neurol Sci 34: 247–265

    Google Scholar 

  • Regland B, Gottfries CG (1992) Slowed synthesis of DNA and methionine is a pathogenic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease? Med Hypothesis 38: 11–19

    Google Scholar 

  • Regland B, Abrahamsson L, Gottfries C-G, Magnus E (1990) Vitamin B12 analogues, homocysteine, methylmalonic acid, and transcobalamins in the study of vitamin B12 deficiency in primary degenerative dementia. Dementia 1: 272–277

    Google Scholar 

  • Regland B, Gottfries C-G, Oreland L (1991) Vitamin B12 induced reduction of platelet monoamine oxidase activity in patients with dementia and pernicious anemia. Eur Arch Psychiatry Clin Neurosci 240: 288–291

    Google Scholar 

  • Reinikainen KJ, Soininen H, Paljärvi L, Riekkinen PJ (1991) Neurotransmitter markers in the cerebrospinal fluid of patients with histologically verified Alzheimer's disease. In: Iqbal K, McLachlan DRC, Wimblad B, Wisniewski HM (eds) Alzheimer's disease: basic mechanisms, diagnosis and therapeutic strategies, pp 526–532

  • Reisberg B, Ferris SH, de Leon MJ (1987) Neuron numbers and dendrite extent in normal aging and Alzheimer's disease. Neurobiol Aging 8: 521–545

    Google Scholar 

  • Roos D, Willanger R (1977) Various degrees of dementia in selected group of gastrectomized patients with low serum B12. Acta Neurol Scand 55: 363–376

    Google Scholar 

  • Roth MS (1980) Ageing of the brain and dementia: an overview. In: Amaducci L, Davison AN, Antuono P (eds) Ageing of the brain and dementia, vol 12. Aging. Raven Press, New York, pp 1–21

    Google Scholar 

  • Sajdel-Sulkowska EM, Marotta CA (1984) Alzheimer's disease brain: alterations in RNA levels and in a ribonuclease-inhibitor complex. Science 225: 947–949

    Google Scholar 

  • Sherif F, Gomes C, Oreland L (1993) Methionine synthase and methionine adenosyltransferase activities in rat brain after ethanol treament. Pharmacol Toxicol 73: 287–290

    Google Scholar 

  • Stabler SP, Marcell PD, Podell ER, Allen RH, Savage DG, Lindenbaum L (1988) Elevation of total homocysteine in the serum of patients with cobalamin or folate deficiency detected by capillary gas chromatography-mass spectrometry. J Clin Invest 81: 466–474

    Google Scholar 

  • Tabor CW, Tabor H (1984) Methionine adenosyltransferase (S-adenosylmethionine synthetase and S-adenosylmethionine descarboxylase. Adv Enzymol Related Areas Mol Biol 56: 251–282

    Google Scholar 

  • Tallan HH (1979) Methionine adenosyltransferase in man: evidence for multiple forms. Biochem Med 21: 129–140

    Google Scholar 

  • Terry RD, Katzman R (1983) Senile dementia of the Alzheimer type: defining a disease. In: Katzman R, Terry RD (eds) The neurology of aging. FA Davis, New York, pp 51–84

    Google Scholar 

  • Tomlinson BE (1977) Morphological changes and dementia in old age. In: Lynn Smith W (ed) Aging and dementia. Spectrum Publications, New York, pp 25–56

    Google Scholar 

  • Volpe JJ, Laster L (1970) Transsulphuration in primate brain: regional distribution of methionine-activating enzyme in the brain of the Rhesus monkey at various stages of development. J Neurochem 17: 413–424

    Google Scholar 

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  1. C. Gomes-Trolin

    Present address: Department of Medical Pharmacology, University of Uppsala, Biomedicum Centrum, Uppsala

Authors and Affiliations

  1. Department of Medical Pharmacology, University of Uppsala, Biomedicum Centrum, Uppsala

    L. Oreland

  2. Department of Psychiatry and Neurochemistry, University of Gothenburg, Sweden

    C. G. Gottfries & B. Regland

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  1. C. Gomes-Trolin
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  2. C. G. Gottfries
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  3. B. Regland
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  4. L. Oreland
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Gomes-Trolin, C., Gottfries, C.G., Regland, B. et al. Influence of vitamin B12 on brain methionine adenosyltransferase activity in senile dementia of the Alzheimer's type. J. Neural Transmission 103, 861–872 (1996). https://doi.org/10.1007/BF01273364

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  • DOI: https://doi.org/10.1007/BF01273364

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