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

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.

SUBMITTER: Hoshi K

PROVIDER: S-EPMC8470343 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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

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

Metabolites 20210910 9

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 M ...[more]

PMID: 34564432

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Dataset Information

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

Publications

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

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