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New methods are needed to quantify myelin integrity in autopsy brain tissues.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>We used polarization\u2010sensitive optical coherence tomography (PS\u2010OCT) to measure bulk tissue relative retardance and birefringence microscopy for high\u2010resolution imaging of myelin degradation. Samples included five AD, five CTE, and four age\u2010matched normal controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>When controlling for age and postmortem interval, no statistically significant differences in white matter retardance or GM myelin defect density were observed between groups. The age difference between controls (64\u00a0\u00b1\u00a04.7 years, mean \u00b1 SD) and disease groups (80.3\u00a0\u00b1\u00a07 years) emerged as an important confounding factor. Amyloid beta and tau staining showed weak correlations with myelin defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>Our label\u2010free approach enables large\u2010volume imaging of brain tissue, a valuable tool for studying myelin changes in neurodegenerative diseases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Multi\u2010modal assessment of myelin integrity using polarization\u2010sensitive optical coherence tomography (PS\u2010OCT) and high\u2010resolution birefringence microscopy.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Age emerged as a critical confounding factor; no significant disease differences were found.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Weak correlation between myelin defects and deposition of amyloid beta\/tau was found in prefrontal gray matter.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Label\u2010free optical methods enable high\u2010resolution, large\u2010volume imaging of myelin.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.70582","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T10:36:16Z","timestamp":1755858976000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Imaging myelin degradation in ex vivo prefrontal cortex tissue blocks in Alzheimer's disease and chronic traumatic encephalopathy"],"prefix":"10.1002","volume":"21","author":[{"given":"Anna","family":"Novoseltseva","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulce","family":"Kureli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaibin","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Electrical &amp; Computer Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiarui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Precious Dominique","family":"Antinew","sequence":"additional","affiliation":[{"name":"Division of Graduate Medical Sciences Chobanian &amp; Avedisian School of Medicine Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Computer Science Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samer","family":"Berghol","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Boston University  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Spurlock","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University Alzheimer's Disease Research Center Boston University CTE Center Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann C.","family":"McKee","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University Alzheimer's Disease Research Center Boston University CTE Center Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"Huber","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston University Alzheimer's Disease Research Center Boston University CTE Center Boston University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology, Athinoula A. 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