Glycan Marker for Idiopathic Normal Pressure Hydrocephalus

Two glycan isoforms of transferrin (Tf), Tf-1 and Tf-2, were found in cerebrospinal fluid (CSF). Tf-1 concentration in CSF was reduced in idiopathic normal pressure hydrocephalus (iNPH), an elderly dementia caused by abnormal metabolism of CSF, whereas Tf-2 concentration was not. The reduction of Tf-1 concentration was not found in Alzheimer’s disease, indicating that Tf-1 can distinguish iNPH from Alzheimer’s disease. Glycan analysis revealed that Tf-1 has unique biantennary asialo- and agalacto-complex N-glycans, which carry bisecting β1,4-GlcNAc and core α1,6-fucose. In contrast, Tf-2 has α2,6-sialylglycan like serum Tf, suggesting that Tf-2 is derived from serum. Tf-1, a glycoform unique to CSF, is speculated to be produced in brain tissue. Immunohistochemistry using anti-Tf antibody on brain tissues revealed that the choroid plexus, which produces CSF, was strongly stained by anti-Tf antibody. These results suggest that Tf-1 is secreted from the choroid plexus and its secretion is reduced by abnormal metabolism of CSF in iNPH.