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Vol. 25, No. 6, 2008
Issue release date: July 2008
Dement Geriatr Cogn Disord 2008;25:516–523

CSF/Serum Folate Gradient: Physiology and Determinants with Special Reference to Dementia

Hagnelius N.-O. · Wahlund L.-O. · Nilsson T.K.
aDepartment of Geriatrics, and bDepartment of Clinical Chemistry, Örebro University Hospital, Örebro, and cDepartment of Clinical Neuroscience, Neurotec, Division of Geriatric Medicine, Neurotec, Karolinska Institutet, Stockholm, Sweden

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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 (RCSF/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 RCSF/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, R2 = 0.518) and to the albumin ratio, a blood-CSF barrier biomarker (β = –0.235). The Alzheimer patients had RCSF/S and albumin ratios similar to the ND subjects. Conclusion: The RCSF/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.

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