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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8470343 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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