{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T04:15:41Z","timestamp":1778300141976,"version":"3.51.4"},"reference-count":62,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T00:00:00Z","timestamp":1757635200000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,9]]},"abstract":"Abstract<\/jats:title>\n \n INTRODUCTION<\/jats:title>\n This study investigates ancestry\u2010specific changes in induced pluripotent stem cell (iPSC)\u2010derived oligodendroglia genomic regulation in Alzheimer's disease (AD), addressing diversity gaps by including African, Amerindian, and European ancestries in the analysis.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n \n We generated 12 iPSC lines from AD patients and controls with different apolipoprotein E (\n APOE<\/jats:italic>\n ) genotypes,\u00a0\n APOE \u03b53\/ \u03b53<\/jats:italic>\n and\n APOE \u03b5<\/jats:italic>\n 4\/ \u03b54<\/jats:italic>\n , across three ancestries. Lines were differentiated into neural spheroids containing oligodendrocyte lineage cells and analyzed by single\u2010nucleus RNA sequencing, Assay for Transposase\u2010Accessible Chromatin with sequencing (ATACseq)APO, and High\u2010throughput Chromosome Conformation Capture (Hi\u2010C).\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n We identified ancestry\u2010specific differences in gene expression and chromatin accessibility of AD genome\u2010wide association study candidate genes.\n APOE \u03b54\/ \u03b54<\/jats:italic>\n carriers across all ancestries showed upregulated cholesterol biosynthesis genes with decreased myelination markers. iPSC\u2010derived oligodendrocytes demonstrated high correlation (\n R<\/jats:italic>\n 2<\/jats:sup>\n \u00a0>\u00a00.85) with human brain transcriptomes.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n Our findings highlight the importance of studying diverse ancestries in AD research and suggest early\n APOE \u03b54<\/jats:italic>\n effects on cholesterol metabolism. The validated iPSC model provides a valuable tool for investigating ancestry\u2010specific disease mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n First study comparing iPSC\u2010derived oligodendroglia across three ancestries.<\/jats:p>\n <\/jats:list-item>\n \n \n APOE \u03b54<\/jats:italic>\n carriers show upregulated cholesterol synthesis in oligodendroglia.\n <\/jats:p>\n <\/jats:list-item>\n \n \n Reduced myelin gene expression observed in\n APOE \u03b54\/\u03b54<\/jats:italic>\n oligodendroglia.\n <\/jats:p>\n <\/jats:list-item>\n \n Ancestry\u2010specific differences found in AD GWAS genes and chromatin states.<\/jats:p>\n <\/jats:list-item>\n \n Novel insights into oligodendrocyte biology relevant to Alzheimer\u2019s disease.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70593","type":"journal-article","created":{"date-parts":[[2025,9,12]],"date-time":"2025-09-12T18:48:17Z","timestamp":1757702897000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ancestral genomic functional differences in oligodendroglia: implications for Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"given":"Aura M.","family":"Ramirez","sequence":"first","affiliation":[{"name":"John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luciana Bertholim","family":"Nasciben","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofia","family":"Moura","sequence":"additional","affiliation":[{"name":"John P. Hussman Institute for Human Genomics University of Miami Miller School of Medicine Miami Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauren","family":"Coombs","sequence":"additional","affiliation":[{"name":"John P. 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