Transferrin biosynthesized by neurons is a diagnostic marker for Alzheimer’s disease

Yasuhiro Hashimoto^1）, Takashi Saito^2）, Yoshiki Yamaguchi^3）, Takashi Honda^4）

^1）Department of Neurosurgery, Fukushima Medical University School of Medicine
^2）Department of Neurocognitive Science, Institute of Brain Science, Nagoya City University Graduate School of Medical Science
^3）Division of Structural Glycobiology, Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University
^4）Department of Human Life Science, Fukushima Medical University School of Nursing

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 isoform, 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.

Address correspondence to Dr. Yasuhiro Hashimoto, Department of Neurosusrgery, Fukushima Medical University School of Medicine （1 Hikarigaoka, Fukushima-City, Fukushima 960-1295, Japan）