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

Author:

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

Abstract

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.

Funder

the Japan Agency for Medical Research and Development

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry,Endocrinology, Diabetes and Metabolism

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