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

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 a...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470343/
https://www.ncbi.nlm.nih.gov/pubmed/34564432
http://dx.doi.org/10.3390/metabo11090616
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author 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
author_facet 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
author_sort Hoshi, Kyoka
collection PubMed
description 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.
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spelling pubmed-84703432021-09-27 Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease 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 Metabolites Article 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. MDPI 2021-09-10 /pmc/articles/PMC8470343/ /pubmed/34564432 http://dx.doi.org/10.3390/metabo11090616 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
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
Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease
title Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease
title_full Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease
title_fullStr Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease
title_full_unstemmed Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease
title_short Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease
title_sort transferrin biosynthesized in the brain is a novel biomarker for alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8470343/
https://www.ncbi.nlm.nih.gov/pubmed/34564432
http://dx.doi.org/10.3390/metabo11090616
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