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

Authors :
Kyoka Hoshi
Hiromi Ito
Eriko Abe
Takashi J. Fuwa
Mayumi Kanno
Yuta Murakami
Mitsunari Abe
Takenobu Murakami
Akioh Yoshihara
Yoshikazu Ugawa
Takashi Saito
Takaomi C. Saido
Kana Matsumoto
Yoshiki Yamaguchi
Katsutoshi Furukawa
Hiroyuki Arai
Mitsuyasu Kanai
Masakazu Miyajima
Hajime Arai
Norihiro Ogawa
Hiroyasu Akatsu
Yoshio Hashizume
Hiroaki Tateno
Takashi Honda
Yasuhiro Hashimoto
Source :
Metabolites, Vol 11, Iss 9, p 616 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

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.

Details

Language :
English
ISSN :
22181989
Volume :
11
Issue :
9
Database :
Directory of Open Access Journals
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
edsdoj.748be030421646a0968d42f71651db55
Document Type :
article
Full Text :
https://doi.org/10.3390/metabo11090616