title: Determinants of the essential one-carbon metabolism metabolites, homocysteine, S-adenosylmethionine, S-adenosylhomocysteine and folate, in cerebrospinal fluid.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry, Metabolic Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Desirée E C
authors.initials: DE
authors.lastname: Smith
authors.forename: Yvo M
authors.initials: YM
authors.lastname: Smulders
authors.forename: Henk J
authors.initials: HJ
authors.lastname: Blom
authors.forename: Julius
authors.initials: J
authors.lastname: Popp
authors.forename: Frank
authors.initials: F
authors.lastname: Jessen
authors.forename: Alexander
authors.initials: A
authors.lastname: Semmler
authors.forename: Melinda
authors.initials: M
authors.lastname: Farkas
authors.forename: Michael
authors.initials: M
authors.lastname: Linnebank
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging; D002851:Chromatography, High Pressure Liquid; D005260:Female; D005492:Folic Acid / Q000097:blood / Q000134:cerebrospinal fluid*; D006710:Homocysteine / Q000134:cerebrospinal fluid*; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D012435:S-Adenosylhomocysteine / Q000134:cerebrospinal fluid*; D012436:S-Adenosylmethionine / Q000134:cerebrospinal fluid*; D053719:Tandem Mass Spectrometry; D014805:Vitamin B 12 / Q000097:blood
chemical_list: D006710:Homocysteine; D012436:S-Adenosylmethionine; D005492:Folic Acid; D012435:S-Adenosylhomocysteine; D014805:Vitamin B 12