{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:46:02Z","timestamp":1790718362079,"version":"4.1.0"},"reference-count":75,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T00:00:00Z","timestamp":1764115200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"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;amp; Dementia"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>We determined whether mitochondrial DNA (mtDNA) depletion induced Alzheimer's disease (AD)\u2010relevant transcription changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Following RNA sequencing (RNA\u2010seq), we identified differentially expressed genes (DEGs) between SH\u2010SY5Y or NT2 mtDNA\u2010depleted (\u03c10) and intact (\u03c1+) cell lines and quantified concordant DEG changes. Gene set enrichment analysis and over\u2010representation analysis were used to determine the impact on the Kyoto Encyclopedia of Genes and Genomes (KEGG) AD and other neurodegenerative disease pathways, ascertain pathway and term enrichment in the Reactome and Gene Ontology databases, and generate Ingenuity Pathway Analysis\n                      <jats:italic>z<\/jats:italic>\n                      \u2010scores.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Relative to their \u03c1+ comparators, \u03c10 lines differentially expressed\u00a0&gt;75% of their genes. The KEGG AD pathway was significantly enriched, and equivalently altered genes ranked the AD, Parkinson's disease, ALS, and Huntington's disease KEGG pathways among the most enriched gene sets. AD\u2010related enriched pathways and terms reflected lipid, insulin signaling, synapse, inflammation\/immune response, endosome\/endocytosis, RNA, and proteostasis biology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>MtDNA depletion alters gene expression in ways that recapitulate or predictably promote AD molecular phenomena.<\/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>MtDNA\u2010depleted neuronal cell lines reshuffle nuclear gene expression.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The KEGG AD pathway is enriched with DEGs.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Transcription\u2010defined pathways and terms relating to AD biology broadly change.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70929","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T08:44:02Z","timestamp":1764146642000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["MtDNA\u2010depleted neuronal cell transcriptomes reveal Alzheimer's disease\u2010related changes"],"prefix":"10.1002","volume":"21","author":[{"given":"Blaise W.","family":"Menta","sequence":"first","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Kansas City Kansas USA"},{"name":"Department of Biochemistry &amp; Molecular Biology 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J.","family":"Andrews","sequence":"additional","affiliation":[{"name":"Department of Psychiatry &amp; Behavioral Sciences University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Kansas City Kansas USA"},{"name":"Department of Biochemistry &amp; Molecular Biology University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Neurology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Pei","sequence":"additional","affiliation":[{"name":"Department of Biostatistics &amp; Data Science University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell 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