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A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH
Authors:Futakawa Satoshi  Nara Kiyomitsu  Miyajima Masakazu  Kuno Atsushi  Ito Hiromi  Kaji Hiroyuki  Shirotani Keiro  Honda Takashi  Tohyama Yuriko  Hoshi Kyoka  Hanzawa Yusuke  Kitazume Shinobu  Imamaki Rie  Furukawa Katsutoshi  Tasaki Kazuhiro  Arai Hiroyuki  Yuasa Tatsuhiko  Abe Masafumi  Arai Hajime  Narimatsu Hisashi  Hashimoto Yasuhiro
Affiliation:Department of Biochemistry, Fukushima Medical University School of Medicine, Fukushima, Japan.
Abstract:Idiopathic normal pressure hydrocephalus (iNPH) is an elderly dementia caused by abnormal metabolism in the cerebrospinal fluid (CSF). The tap test is the current basis for confirming iNPH, but it shows very low sensitivity, indicating that many patients who might be cured by a shunt operation will be missed. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we found two transferrin isoforms: one had a unique N-glycan (Tf-1) whereas the other had N-glycan similar to that of serum transferrin (Tf-2). Glycan analyses revealed that Tf-1 had branching (biantennary) asialo- and agalacto-complex type N-glycans (N-acetylglucosamine [GlcNAc]-terminated glycans), which carried bisecting β1,4-N-acetylglucosamine and core α1,6-fucose. To examine glycoform whether changes in iNPH, we introduced the Tf-2/Tf-1 ratio as a diagnostic index, which minimized blot-to-blot variations in measurement. The Tf-2/Tf-1 ratios of iNPH patients are significantly higher than those of controls (p = 0.0019) and Alzheimer's patients (p = 0.0010). This suggests that the Tf-2/Tf-1 ratio could distinguish iNPH from Alzheimer's disease, and possibly other dementias. In conclusion, glycoform analysis has diagnostic potential in neurological diseases.
Keywords:N-glycan   Transferrin   Glycosylation   Cerebrospinal fluid   Choroid plexus   Dementia   Idiopathic normal pressure hydrocephalus   Alzheimer's disease   Biomarker
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