A unique N-glycan on human transferrin in CSF: A possible biomarker for iNPH

Satoshi Futakawa, Kiyomitsu Nara, Masakazu Miyajima, Atsushi Kuno, Hiromi Ito, Hiroyuki Kaji, Keiro Shirotani, Takashi Honda, Yuriko Tohyama, Kyoka Hoshi, Yusuke Hanzawa, Shinobu Kitazume, Rie Imamaki, Katsutoshi Furukawa, Kazuhiro Tasaki, Hiroyuki Arai, Tatsuhiko Yuasa, Masafumi Abe, Hajime Arai, Hisashi NarimatsuYasuhiro Hashimoto

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1807-1815
Number of pages9
JournalNeurobiology of Aging
Volume33
Issue number8
DOIs
Publication statusPublished - 2012 Aug

Keywords

  • Alzheimer's disease
  • Biomarker
  • Cerebrospinal fluid
  • Choroid plexus
  • Dementia
  • Glycosylation
  • Idiopathic normal pressure hydrocephalus
  • N-glycan
  • Transferrin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Clinical Neurology
  • Geriatrics and Gerontology

Fingerprint

Dive into the research topics of 'A unique N-glycan on human transferrin in CSF: A possible biomarker for iNPH'. Together they form a unique fingerprint.

Cite this