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Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid

Smith, Desirée E.C. ; Smulders, Yvo M. ; Blom, Henk J. ; Popp, Julius ; Jessen, Frank ; Semmler, Alexander ; Farkas, Melinda ; Linnebank, Michael

In: Clinical Chemistry and Laboratory Medicine (CCLM), 2012, vol. 50, no. 9, p. 1641-1647

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    Title
    • Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid
    Author
    • Smith, Desirée E.C.. Department of Clinical Chemistry, Metabolic Laboratory, VU University Medical Center, Amsterdam, The Netherlands
    • Smulders, Yvo M.
    • Blom, Henk J.
    • Popp, Julius
    • Jessen, Frank. Department of Psychiatry, University Hospital Bonn, Bonn, Germany
    • Semmler, Alexander. Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    • Farkas, Melinda. Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    • Linnebank, Michael. Department of Neurology, University Hospital Zurich, Zurich, Switzerland
    Document Type
    • Postprint
    Language
    • English
    Published in
    • Clinical Chemistry and Laboratory Medicine (CCLM), 2012, vol. 50, no. 9, p. 1641-1647. Walter de Gruyter
    Other Version
    OAI-PMH Identifier
    • oai:doc.rero.ch:299329
    Summary
    Background: Disturbances in the levels of one-carbon (1C) metabolism metabolites have been associated with a wide variety of neuropsychiatric diseases. Cerebrospinal fluid (CSF) levels of homocysteine (Hcy) and the other 1C metabolites, nor their interrelatedness and putative determinants, have been studied extensively in a healthy population. Methods: Plasma and CSF samples from 100 individuals free from neuropsychiatric diseases were analyzed (55 male, 45 female; age 50±17 years). In blood, we measured plasma Hcy, serum folate and serum vitamin B12. In CSF, we measured total Hcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH) and 5-methyltetrahydrofolate (5-methylTHF). Highly selective analytical methods like liquid chromatography combined with either mass spectrometry or fluorescence detection were used. Results: CSF Hcy was inversely correlated with CSF 5-methylTHF and positively with plasma Hcy, independent of serum folate status. CSF SAH correlated with age, lower CSF 5-methylTHF and higher CSF Hcy. CSF 5-methylTHF showed independent negative correlations with age and positive correlations with serum folate. CSF SAM did not correlate with any of the 1C metabolites. Conclusions: Aging is characterized by a reduction in CSF 5-methylTHF levels and increased CSF levels of the potentially neurotoxic transmethylation inhibitor SAH. CSF 5-methylTHF, which is itself determined in part by systemic folate status, is a powerful independent determinant of CSF levels of Hcy and SAH