A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH
A unique N-glycan on human transferrin in CSF: a possible biomarker for iNPH
复制标题
DOI：
10.1016/j.neurobiolaging.2011.02.023
复制
发表时间：
2012-08-01
影响因子：
4.2
通讯作者：
Hashimoto, Yasuhiro
中科院分区：
文献类型：
--
作者：
Futakawa, Satoshi;Nara, Kiyomitsu;Hashimoto, Yasuhiro
特发性正常压力脑积水（Idiopathic normal pressure hydrocephalus，iNPH）是一种由脑脊液（cerebralfluid，CSF）代谢异常引起的老年痴呆。抽头测试是目前确认iNPH的基础，但它显示出非常低的敏感性，这表明许多可能通过分流手术治愈的患者将被遗漏。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳上，我们发现了两种转铁蛋白亚型：一种具有独特的N-聚糖（Tf-1），而另一种具有与血清转铁蛋白相似的N-聚糖（Tf-2）。聚糖分析显示，Tf-1具有分支（双触角）脱唾液酸和无半乳糖复合物型N-聚糖（N-乙酰葡糖胺[GlcNAc]-末端聚糖），其携带二等分β 1，4-N-乙酰葡糖胺和核心α 1，6-岩藻糖。为了检查糖型是否在iNPH中变化，我们引入了Tf-2/Tf-1比率作为诊断指标，其最小化了测量中的印迹间差异。iNPH患者的Tf-2/Tf-1比值显著高于对照组（p = 0.0019）和阿尔茨海默病患者（p = 0.0010）。这表明Tf-2/Tf-1比值可以将iNPH与阿尔茨海默病以及可能的其他痴呆症区分开来。总之，糖型分析在神经系统疾病中具有诊断潜力。(C)2012年由Elsevier Inc.出版
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.