期刊
NEUROBIOLOGY OF AGING
卷 33, 期 8, 页码 1807-1815出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.02.023
关键词
N-glycan; Transferrin; Glycosylation; Cerebrospinal fluid; Choroid plexus; Dementia; Idiopathic normal pressure hydrocephalus; Alzheimer's disease; Biomarker
资金
- New Energy and Industrial Technology Development Organization (NEDO) of Japan
- Ministry of Health, Labor and Welfare of Japan [2006-Nanchi-Ippan-017]
- Naito Foundation
- Ministry of Education, Science, Sports and Culture of Japan [20023023]
- Japan Science and Technology Agency
- Grants-in-Aid for Scientific Research [20023023] Funding Source: KAKEN
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 beta 1,4-N-acetylglucosamine and core alpha 1,6-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. (C) 2012 Published by Elsevier Inc.
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