{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T19:16:40Z","timestamp":1791487000851,"version":"4.3.4"},"reference-count":36,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Japan Agency for Medical Research and Development (AMED)","award":["18hm0102042h0001, 18hm0102042h0002, 18hm0102042h0003"],"award-info":[{"award-number":["18hm0102042h0001, 18hm0102042h0002, 18hm0102042h0003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3390\/metabo11090616","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T10:31:34Z","timestamp":1631269894000},"page":"616","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Transferrin Biosynthesized in the Brain Is a Novel Biomarker for Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"11","author":[{"given":"Kyoka","family":"Hoshi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eriko","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi J.","family":"Fuwa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Kanno","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuta","family":"Murakami","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3913-2292","authenticated-orcid":false,"given":"Mitsunari","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9042-5309","authenticated-orcid":false,"given":"Takenobu","family":"Murakami","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Tottori 683-8504, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akioh","family":"Yoshihara","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Ugawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Saito","sequence":"additional","affiliation":[{"name":"Laboratory of Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takaomi C.","family":"Saido","sequence":"additional","affiliation":[{"name":"Laboratory of Proteolytic Neuroscience, RIKEN Center for Brain Science, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Structural Glycobiology Team, RIKEN Global Research Cluster, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0100-5439","authenticated-orcid":false,"given":"Yoshiki","family":"Yamaguchi","sequence":"additional","affiliation":[{"name":"Structural Glycobiology Team, RIKEN Global Research Cluster, Saitama 351-0198, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Institute of Development, Aging and Cancer, Tohoku University, Miyagi 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Arai","sequence":"additional","affiliation":[{"name":"Institute of Development, Aging and Cancer, Tohoku University, Miyagi 980-8575, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuyasu","family":"Kanai","sequence":"additional","affiliation":[{"name":"Division of Neurology, Mihara Memorial Hospital, Gunma 372-0006, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Miyajima","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Arai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Juntendo University, Tokyo 113-8421, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Fukushimura Hospital, Aichi 441-8124, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0089-6033","authenticated-orcid":false,"given":"Hiroyasu","family":"Akatsu","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Fukushimura Hospital, Aichi 441-8124, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Hashizume","sequence":"additional","affiliation":[{"name":"Department of Neuropathology, Fukushimura Hospital, Aichi 441-8124, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Tateno","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Biotechnology Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Ibaraki 305-8560, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Honda","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, 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