“Brain-type” transferrin as a novel biomarker for altered cerebrospinal fluid production

Abstract

Iron is an essential nutrient for myelination, neurotransmission and electron transfer in the respiratory chain. Transferrin (Tf), an iron transporter, is mainly biosynthesized in the liver, but Tf is also biosynthesized in the brain; i.e., oligodendrocytes some neurons, and choroid plexus, a cerebrospinal fluid (CSF) producing tissue. CSF contains two glycan isoforms of Tf: brain-type Tf and serum-type Tf. Brain-type Tf is uniquely glycolsylated with biantennary asialo- and agalacto-complex type N-glycans that carry bisecting β1,4-GlcNAc and core α1,6-Fuc. The glycans of serum-type Tf are similar to those of serum transferrin. We speculate that brain-type Tf could be a biomarker of altered CSF production based on the following observations: (i) choroid plexus epithelial cells highly express Tf which carries N-acetylglucosamine-terminated glycans, (ii) brain-type Tf decreases in idiopathic normal pressure hydrocephalus (iNPH), in which CSF production is suspected to decrease, and (iii) brain-type Tf increases in spontaneous intracranial hypotension (SIH), in which CSF production is suspected to increase. Thus brain-type Tf could be a useful biomarker for CSF-related abnormalities.