{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:29:46Z","timestamp":1778754586491,"version":"3.51.4"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011611","name":"Shinshu Public Utility Foundation for Promotion of Medical Sciences","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100011611","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Apolipoprotein (apo) E is the major cholesterol carrier in the central nervous system (CNS); however, the clinical relevance of its cysteine-thiol redox status in cerebrospinal fluid (CSF) remains unclear. We investigated whether CSF apoE redox indices (redox-IDX-apoE) reflect cholesterol transport efficiency and disease-specific pathologies. We quantified reduced (red), reversibly oxidized (roxi), and irreversibly oxidized (oxi) apoE in CSF and serum using a maleimide-based band-shift assay. We analyzed relationships between redox-IDX-apoE, CSF cholesterol (TC) level, and the TC\/apoE ratio (inverse transport efficiency) in patients with apoE3\/E3 and identified transport determinants using isometric log-ratio (ILR) regression. Significant but only moderate correlations between CSF and serum indices suggested distinct redox behavior in the two compartments. ApoE3\/E4 carriers exhibited higher oxi-apoE, reflecting reduced buffering capacity. In apoE3\/E3 CSF, aging increased roxi\/total and decreased red\/roxi, suggesting a shift toward oxidized forms. CSF TC levels positively correlated with roxi-related indices. Conversely, the TC\/apoE ratio negatively correlated with red\/roxi, indicating that red-apoE supports higher efficiency. ILR analysis confirmed that maintaining the reduced monomeric state, rather than the reversibly oxidized form, was independently associated with improved transport efficiency. Diagnostic groups exhibited distinct signatures: neurodegenerative disorders showed elevated irreversible oxidation, whereas neuroimmunological and infectious conditions exhibited profiles suggestive of reversible and acute oxidation, respectively. The CSF apoE redox status links local redox balance to cholesterol handling and reflects CNS pathophysiology. Maintaining reduced cysteine-thiol appears important for functional capacity, whereas a shift toward oxidation reflects a trade-off between buffering ability and transport efficiency. These indices may serve as potential biomarkers.<\/jats:p>","DOI":"10.1042\/bsr20250388","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T14:59:39Z","timestamp":1776783579000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox status of apolipoprotein E in cerebrospinal fluid: a mechanistically informative biomarker for central nervous system disorders"],"prefix":"10.1042","volume":"46","author":[{"given":"Yui","family":"Uematsu","sequence":"first","affiliation":[{"name":"1Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wakana","family":"Iinuma","sequence":"additional","affiliation":[{"name":"1Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riho","family":"Shimizu","sequence":"additional","affiliation":[{"name":"1Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"2Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroto","family":"Matsuura","sequence":"additional","affiliation":[{"name":"1Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"2Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsuneaki","family":"Yoshinaga","sequence":"additional","affiliation":[{"name":"3Department of Neurology and Rheumatology, Shinshu University, Matsumoto, Japan"},{"name":"4Division of NeuroHealth Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahide","family":"Yazaki","sequence":"additional","affiliation":[{"name":"4Division of NeuroHealth Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan"},{"name":"5Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3666-2455","authenticated-orcid":false,"given":"Kazuyoshi","family":"Yamauchi","sequence":"additional","affiliation":[{"name":"1Department of Clinical Laboratory Investigation, Graduate School of Medicine, Shinshu University, Matsumoto, Japan"},{"name":"4Division of NeuroHealth Innovation, Institute for Biomedical Sciences, Shinshu University, Matsumoto, Japan"},{"name":"5Department of Biomedical Laboratory Sciences, School of Health Sciences, Shinshu University, Matsumoto, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026051405561186700_B1","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1126\/science.3283935","article-title":"Apolipoprotein E: cholesterol transport protein with expanding role in cell biology","volume":"240","author":"Mahley","year":"1988","journal-title":"Science"},{"key":"2026051405561186700_B2","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1146\/annurev.genom.1.1.507","article-title":"Apolipoprotein E: far more than a lipid transport protein","volume":"1","author":"Mahley","year":"2000","journal-title":"Annu. 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