Taniguchi Miyako, Okayama Yuka, Hashimoto Yuki, Kitaura Miki, Jimbo Daiki, Wakutani Yosuke, Wada-Isoe Kenji, Nakashima Kenji, Akatsu Hiroyasu, Furukawa Katsutoshi, Arai Hiroyuki, Urakami Katsuya
Department of Biological Regulation, School of Health Sciences, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan.
Dement Geriatr Cogn Disord. 2008;26(2):117-22. doi: 10.1159/000147479. Epub 2008 Jul 24.
BACKGROUND/AIMS: Alzheimer's disease (AD) is a well-known type of dementia. However, it remains difficult to identify AD in the early stage and to distinguish it from other dementing disorders. We examined glycoproteins in cerebrospinal fluid (CSF) as potential biological markers of AD.
CSF samples were collected from AD, other dementia and nondemented patients. Glycoproteins in CSF were detected by lectin blotting using wheat germ agglutinin (WGA), and sugar chain analysis was performed by isoelectric focusing.
In Alzheimer's CSF, several glycoproteins had lower WGA-binding activities, one of which was sufficiently sensitive and specific to distinguish AD from nondemented controls and other dementias. Further analysis identified this glycosylated protein as transferrin, and altered sugar chain composition of transferrin isoforms was observed despite normal protein levels in CSF.
The decreased WGA-binding activity of transferrin in AD is probably due to altered glycosylation of transferrin molecules. Transferrin glycosylation is thus a potential biological marker for AD diagnosis, and changes in this glycosylation may play an important role in the pathophysiology of AD.
背景/目的：阿尔茨海默病（AD）是一种广为人知的痴呆类型。然而，早期识别AD并将其与其他痴呆性疾病区分开来仍然很困难。我们检测了脑脊液（CSF）中的糖蛋白，将其作为AD潜在的生物学标志物。
从AD患者、其他痴呆患者和非痴呆患者中收集脑脊液样本。使用麦胚凝集素（WGA）通过凝集素印迹法检测脑脊液中的糖蛋白，并通过等电聚焦进行糖链分析。
在阿尔茨海默病患者的脑脊液中，几种糖蛋白的WGA结合活性较低，其中一种对区分AD与非痴呆对照及其他痴呆具有足够的敏感性和特异性。进一步分析确定这种糖基化蛋白为转铁蛋白，尽管脑脊液中蛋白质水平正常，但观察到转铁蛋白异构体的糖链组成发生了改变。
AD中转铁蛋白的WGA结合活性降低可能是由于转铁蛋白分子糖基化改变所致。因此，转铁蛋白糖基化是AD诊断的潜在生物学标志物，这种糖基化的变化可能在AD的病理生理学中起重要作用。
