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However, the mechanisms that lead to the degeneration of these neurons are not known.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Single\u2010nucleus gene expression and Assay for Transposase\u2010Accessible Chromatin\u00a0(ATAC)\u00a0sequencing were performed on postmortem human basal forebrain from unaffected control and DS tissue samples at 0\u20132 years of age (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a04 each).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Sequencing analysis of postmortem human basal forebrain identifies gene expression differences in DS early in life. Genes encoding proteins associated with energy metabolism pathways, specifically oxidative phosphorylation and glycolysis, and genes encoding antioxidant enzymes are upregulated in DS BFCNs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Multiomic analyses reveal that energy metabolism may be disrupted in DS BFCNs by birth. Increased oxidative phosphorylation and the accumulation of reactive oxygen species byproducts may be early contributors to DS BFCN neurodegeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>First multiomic gene expression and ATAC analysis of human basal forebrain.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Basal forebrain pathology in DS begins by birth.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cell type proportions are altered in early postnatal DS basal forebrain.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Gene expression suggests dysregulated energy metabolism in DS BFCNs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Genes encoding oxidative phosphorylation subunits and glycolysis enzymes are dysregulated in DS BFCNs.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70445","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T04:45:17Z","timestamp":1752727517000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Single\u2010nucleus analysis reveals oxidative stress in Down syndrome basal forebrain neurons at birth"],"prefix":"10.1002","volume":"21","author":[{"given":"Nicole R.","family":"West","sequence":"first","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Cellular and Molecular Biology Graduate Program University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana Hanthanan","family":"Arachchilage","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Knaack","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawn","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masoumeh","family":"Hosseini","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan D.","family":"Risgaard","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Medical Scientist Training Program University of Wisconsin\u2010Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pubudu","family":"Kumarage","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Martinez","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su\u2010Chun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Center for Neurologic Diseases Sanford Burnham Prebys Medical Discovery Institute  San Diego California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daifeng","family":"Wang","sequence":"additional","affiliation":[{"name":"Waisman Center University of Wisconsin\u2010Madison  Madison Wisconsin USA"},{"name":"Department of Biostatistics and Medical Informatics University of Wisconsin\u2010Madison School of Medicine and Public Health  Madison Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre M. 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