CSF/Serum folate gradient: Physiology and determinants with special reference to dementia

Background: Folate depletion has been implicated as a risk factor for neurodegenerative disorders. We hypothesized that transport of folate to the cerebrospinal fluid (CSF) compartment could be involved in the pathophysiology of these disorders. Methods: The CSF/serum folate gradient (R-CSF/S) was studied in 205 subjects with suspected cognitive disorder. Its relation to clinical and biochemical indices, including the integrity of the blood-CSF barrier, were characterized. Results: In subjects who were diagnosed as nondemented (ND) the mean R-CSF/S +/- SD was 2.46 +/- 0.62 versus 2.09 +/- 0.67 (p = 0.008) in the dementia subgroup with a vascular component (VaD + mixed). The ND subgroup had higher CSF folate (p = 0.001) and lower serum homocysteine values (p = 0.001) than the VaD + mixed subgroup. The folate gradient RCSF/S was negatively correlated with serum folate (p < 0.001, R-2 = 0.518) and to the albumin ratio, a blood-CSF barrier biomarker (beta = -0.235). The Alzheimer patients had R-CSF/S and albumin ratios similar to the ND subjects. Conclusion: The R-CSF/S was significantly lower in the VaD + mixed dementia subgroup, suggestive of a defect in the transport of folate over the choroid plexus that seems to be characteristic of, and limited to, the VaD + mixed dementia subgroup. Copyright (C) 2008 S. Karger AG, Basel.