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

Abstract

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 R_CSF/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 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.

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

“…Another study (18) showed similar results, while a further one (9) observed higher folate serum levels than in our population and lower CSF levels. However, this last study did not use multi vitamin intake as an exclusion criteria.…”

Folate and Homocysteine in the Cerebrospinal Fluid of Patients with Alzheimer’s Disease or Dementia: A Case Control Study

“…Decreased folate and increased Hcy levels were also associated with changes in brain structures detected by imaging [30,31]. According to previous works [24,32,33] reported in table 4, plasma Hcy was slightly increased in both AD and nAD patients compared to control subjects matched for age, but the difference did not reach significance, probably because the groups’ size was rather small in our study or because the controls were not healthy subjects.…”

“…Likewise, the hypothesis that Hcy was a risk factor has been suggested by the observation of increased concentrations in plasma or serum from patients with AD [18,21]. Some studies have been published showing that the concentration of CSF folate was lower in AD patients compared to subjects without dementia [22,23,24,25]. Similarly, CSF Hcy was assayed in some studies including patients with AD and control subjects [25,26,27].…”

Fibrinolysis and von Willebrand factor in Alzheimer's disease and vascular dementia – a case-referent study

“…From 1996-98 onwards, the hyperhomocysteinemic aspect of VaD (and AD) has attracted attention [33][34][35][36] An increase in hs-CRP may probably per se cause increased plasma tPA concentrations [29]. In our study we have shown ( Table 1) that hs-CRP is significantly lower in AD Table 2 were adjusted for hs-CRP.…”