大脑中生物合成的转铁蛋白是阿尔茨海默病的一种新型生物标志物。

Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer's Disease.

作者信息

Hoshi Kyoka, Ito Hiromi, Abe Eriko, Fuwa Takashi J, Kanno Mayumi, Murakami Yuta, Abe Mitsunari, Murakami Takenobu, Yoshihara Akioh, Ugawa Yoshikazu, Saito Takashi, Saido Takaomi C, Matsumoto Kana, Yamaguchi Yoshiki, Furukawa Katsutoshi, Arai Hiroyuki, Kanai Mitsuyasu, Miyajima Masakazu, Arai Hajime, Ogawa Norihiro, Akatsu Hiroyasu, Hashizume Yoshio, Tateno Hiroaki, Honda Takashi, Hashimoto Yasuhiro

机构信息

Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan.

Department of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.

出版信息

Metabolites. 2021 Sep 10;11(9):616. doi: 10.3390/metabo11090616.

Glycosylation is a cell type-specific post-translational modification that can be used for biomarker identification in various diseases. Aim of this study is to explore glycan-biomarkers on transferrin (Tf) for Alzheimer's disease (AD) in cerebrospinal fluid (CSF). Glycan structures of CSF Tf were analyzed by ultra-performance liquid chromatography followed by mass spectrometry. We found that a unique mannosylated-glycan is carried by a Tf isoform in CSF (Man-Tf). The cerebral cortex contained Man-Tf as a major isofom, suggesting that CSF Man-Tf is, at least partly, derived from the cortex. Man-Tf levels were analyzed in CSF of patients with neurological diseases. Concentrations of Man-Tf were significantly increased in AD and mild cognitive impairment (MCI) comparing with other neurological diseases, and the levels correlated well with those of phosphorylated-tau (p-tau), a representative AD marker. Consistent with the observation, p-tau and Tf were co-expressed in hippocampal neurons of AD, leading to the notion that a combined p-tau and Man-Tf measure could be a biomarker for AD. Indeed, levels of p-tau x Man-Tf showed high diagnostic accuracy for MCI and AD; 84% sensitivities and 90% specificities for MCI and 94% sensitivities and 89% specificities for AD. Thus Man-Tf could be a new biomarker for AD.

糖基化是一种细胞类型特异性的翻译后修饰，可用于多种疾病的生物标志物识别。本研究的目的是探索脑脊液（CSF）中用于阿尔茨海默病（AD）的转铁蛋白（Tf）上的聚糖生物标志物。采用超高效液相色谱-质谱联用技术分析脑脊液Tf的聚糖结构。我们发现脑脊液中的一种Tf异构体携带一种独特的甘露糖基化聚糖（Man-Tf）。大脑皮层以Man-Tf作为主要异构体，这表明脑脊液中的Man-Tf至少部分来源于皮层。分析了神经疾病患者脑脊液中的Man-Tf水平。与其他神经疾病相比，AD和轻度认知障碍（MCI）患者脑脊液中Man-Tf的浓度显著升高，且其水平与代表性AD标志物磷酸化tau蛋白（p-tau）的水平密切相关。与该观察结果一致，p-tau和Tf在AD患者的海马神经元中共表达，这表明联合检测p-tau和Man-Tf可能是AD的一种生物标志物。事实上，p-tau×Man-Tf水平对MCI和AD具有较高的诊断准确性；对MCI的敏感性为84%，特异性为90%；对AD的敏感性为94%，特异性为89%。因此，Man-Tf可能是AD的一种新生物标志物。