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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-09-01
|
| Series: | Metabolites |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2218-1989/11/9/616 |
| _version_ | 1797518215938572288 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Kyoka Hoshi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T07:27:01Z |
| format | Article |
| id | doaj.art-748be030421646a0968d42f71651db55 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T07:27:01Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-748be030421646a0968d42f71651db552023-11-22T14:11:49ZengMDPI AGMetabolites2218-19892021-09-0111961610.3390/metabo11090616Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s DiseaseKyoka Hoshi0Hiromi Ito1Eriko Abe2Takashi J. Fuwa3Mayumi Kanno4Yuta Murakami5Mitsunari Abe6Takenobu Murakami7Akioh Yoshihara8Yoshikazu Ugawa9Takashi Saito10Takaomi C. Saido11Kana Matsumoto12Yoshiki Yamaguchi13Katsutoshi Furukawa14Hiroyuki Arai15Mitsuyasu Kanai16Masakazu Miyajima17Hajime Arai18Norihiro Ogawa19Hiroyasu Akatsu20Yoshio Hashizume21Hiroaki Tateno22Takashi Honda23Yasuhiro Hashimoto24Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Biochemistry, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Biochemistry, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Biochemistry, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Neurosurgery, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Neurology, Fukushima Medical University, Fukushima 960-1295, JapanDivision of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, JapanDepartment of Neurology, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Neurology, Fukushima Medical University, Fukushima 960-1295, JapanLaboratory of Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama 351-0198, JapanLaboratory of Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama 351-0198, JapanStructural Glycobiology Team, RIKEN Global Research Cluster, Saitama 351-0198, JapanStructural Glycobiology Team, RIKEN Global Research Cluster, Saitama 351-0198, JapanInstitute of Development, Aging and Cancer, Tohoku University, Miyagi 980-8575, JapanInstitute of Development, Aging and Cancer, Tohoku University, Miyagi 980-8575, JapanDivision of Neurology, Mihara Memorial Hospital, Gunma 372-0006, JapanDepartment of Neurosurgery, Juntendo University, Tokyo 113-8421, JapanDepartment of Neurosurgery, Juntendo University, Tokyo 113-8421, JapanDepartment of Neuropathology, Fukushimura Hospital, Aichi 441-8124, JapanDepartment of Neuropathology, Fukushimura Hospital, Aichi 441-8124, JapanDepartment of Neuropathology, Fukushimura Hospital, Aichi 441-8124, JapanCellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8560, JapanDepartment of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, JapanDepartment of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, JapanGlycosylation 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.https://www.mdpi.com/2218-1989/11/9/616Alzheimer’s diseasecerebrospinal fluidbiomarkertransferringlycan-isoforms |
| spellingShingle | 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 Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer’s Disease Metabolites Alzheimer’s disease cerebrospinal fluid biomarker transferrin glycan-isoforms |
| 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 | Alzheimer’s disease cerebrospinal fluid biomarker transferrin glycan-isoforms |
| url | https://www.mdpi.com/2218-1989/11/9/616 |
| work_keys_str_mv | AT kyokahoshi transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT hiromiito transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT erikoabe transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT takashijfuwa transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT mayumikanno transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT yutamurakami transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT mitsunariabe transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT takenobumurakami transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT akiohyoshihara transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT yoshikazuugawa transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT takashisaito transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT takaomicsaido transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT kanamatsumoto transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT yoshikiyamaguchi transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT katsutoshifurukawa transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT hiroyukiarai transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT mitsuyasukanai transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT masakazumiyajima transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT hajimearai transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT norihiroogawa transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT hiroyasuakatsu transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT yoshiohashizume transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT hiroakitateno transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT takashihonda transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease AT yasuhirohashimoto transferrinbiosynthesizedinthebrainisanovelbiomarkerforalzheimersdisease |