TY - JOUR
T1 - A unique N-glycan on human transferrin in CSF
T2 - A possible biomarker for iNPH
AU - Futakawa, Satoshi
AU - Nara, Kiyomitsu
AU - Miyajima, Masakazu
AU - Kuno, Atsushi
AU - Ito, Hiromi
AU - Kaji, Hiroyuki
AU - Shirotani, Keiro
AU - Honda, Takashi
AU - Tohyama, Yuriko
AU - Hoshi, Kyoka
AU - Hanzawa, Yusuke
AU - Kitazume, Shinobu
AU - Imamaki, Rie
AU - Furukawa, Katsutoshi
AU - Tasaki, Kazuhiro
AU - Arai, Hiroyuki
AU - Yuasa, Tatsuhiko
AU - Abe, Masafumi
AU - Arai, Hajime
AU - Narimatsu, Hisashi
AU - Hashimoto, Yasuhiro
N1 - Funding Information:
We thank Ms. Kaori Hagita, Yukari Saito, and Kazuko Hashimoto for secretarial assistances, Prof. Tatsuya Okada for advice on the statistical analysis, and Dr. Kenneth Nollet for critically reading the manuscript. We sincerely acknowledge our colleagues in the Hashimoto laboratories for valuable discussions. This work was supported by the New Energy and Industrial Technology Development Organization (NEDO) of Japan. Yasuhiro Hashimoto was the recipient of a grant from the Ministry of Health, Labor and Welfare of Japan (grant number 2006-Nanchi-Ippan-017 ); the Naito Foundation; the Ministry of Education, Science, Sports and Culture of Japan (grant number 20023023 ), and the Japan Science and Technology Agency (A-step grant).
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Biomarker
KW - Cerebrospinal fluid
KW - Choroid plexus
KW - Dementia
KW - Glycosylation
KW - Idiopathic normal pressure hydrocephalus
KW - N-glycan
KW - Transferrin
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UR - http://www.scopus.com/inward/citedby.url?scp=84861861870&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2011.02.023
DO - 10.1016/j.neurobiolaging.2011.02.023
M3 - Article
C2 - 21459485
AN - SCOPUS:84861861870
SN - 0197-4580
VL - 33
SP - 1807
EP - 1815
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 8
ER -