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RESEARCH PAPER / 2025-05-30

A highly sensitive quantitative method of polysialic acid reveals its unique changes in brain aging and neuropsychiatric disorders.

Masaya Hane, Ayane Naramura, Kaito Hayakawa, Chikara Abe, Takahiro Nakagawa, Itaru Kushima, Soma Furukawa, Yuki Fukami, Keisuke Ikegami, Kazumasa Saigoh, Susumu Kusunoki, Masahisa Katsuno, Norio Ozaki, Ken Kitajima, Chihiro Sato

Integrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, 464-8601, Japan.Integrated Glyco-Biomedical Research Center (iGMED), Institute for Glyco-core Research (iGCORE), Nagoya University, Nagoya, 464-8601, Japan. · pubmed

Abstract

Polysialic acid (polySia), a glycoepitope critical for neural development and plasticity, remains difficult to quantify owing to its structural complexity. Here, we present a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) utilizing novel probes to measure polySia expression. Using this method, we quantified polySia levels in mouse brain samples across various developmental and aging stages. Notable age-related changes were observed, particularly in neuroplastic regions such as the hippocampus and olfactory bulb, where polySia levels increased at 12 months, potentially reflecting resilience mechanisms against brain aging. Elevated polySia levels in blood samples were also detected in both a schizophrenia mouse model and human patients, with a notable male preponderance. In contrast, no significant changes were observed in patients with chronic inflammatory demyelinating polyneuropathy. These findings, enabled by the novel probes, highlight a potential role for polySia in brain aging and neuropsychiatric disorders, offering new insights into developmental and disease mechanisms and supporting its utility as a diagnostic biomarker for brain impairments.

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Research summary

The paper claims that polysialic acid levels change significantly with aging and in neuropsychiatric disorders, suggesting its potential role as a biomarker for brain impairments. The research addresses changes in a glycoepitope associated with neural plasticity and aging, which could provide insights into mechanisms underlying age-related cognitive decline.

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