CSF homocysteine, CSF folates and choroid plexus

Abstract

Selley et al. [9] recently reported an increase of homocysteine and (E)-4-hydroxy-2-nonenal (HNE) levels associated with a decrease of folate levels in plasma and cerebrospinal fluid (CSF) of Alzheimer’s disease (AD) patients. These results and their interpretation should be considered in our opinion in the light of the functions of the blood–brain barrier, particularly at the level of choroid plexuses (CPs). CSF is not formed by a simple passive process of ultrafiltration. About 90% of CSF is actively secreted by CP, the remaining 10% coming from brain interstitial fluid drainage [10]. Folate and vitamin B12 do not diffuse from blood to CSF, but are actively transported in CP [16]. Usually transporters are saturated at half-level, in case of shortage, a recruitement can occur to prevent variations of CSF levels [16]. Folate CSF levels are two of three times (14–18 ng/ml) folate blood levels (3–12 ng/ml) [7,13]. In exceptional cases of alteration of choroid plexus transporter, folate CSF levels are very low while serum levels remain normal [17]. In the reported study by Selley, CSF folate levels in controls are remarkably lower than serum levels, which is in opposition to what is classically reported in the literature [7,13]; this discrepancy could explain the absence of a significant correlation between the increase of homocysteine CSF levels and the decrease of CSF folate in AD patients. CSF amino acid levels are only 40% of plasma levels, being actively transported to CSF through an active mechanism at CP level [5]. Four amino acid transporters have been described, two for large and small amino acids and two for cationic and anionic amino acids [11].