Biomarkers of folate and vitamin B12 status in cerebrospinal fluid

Folate and vitamin B-12 are essential cofactors for the methionine/homocysteine cycle in the brain. These vitamins mediate the remethylation of homocysteine (Hcy), which affects the production of the universal methyl donor, S-adenosylmethionine (SAM), in the brain among other organs. Additionally, increase plasma concentrations of total Hcy (tHcy) are associated with cerebrovascular disease and can compromise the blood-brain barrier. tHcy concentrations in the brain and cerebrospinal fluid become increased in several psychiatric and neurological disorders. Disturbances in the transmethylation pathway indicate by abnormal SAM, S-adenosylhomocysteine or their ratio have been reported in many neurodegenerative diseases, such as dementia, depression or Parkinson's disease. Cobalamin is essential for neuronal generation and its deficiency can cause degeneration of the nervous system. Available data emphasize that deficiency of folate and vitamin B-12 can lead to elevated concentrations of tHcy and disturbed methylation potential in the brain. Therefore, acquired or inherited disorders in these metabolic pathways are associated with brain abnormalities and severe neurological symptoms that are mostly irreversible, even after providing the missing cofactors. This review discusses the relationship between brain and blood levels of key vitamins and metabolites related to one carbon metabolism.