{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:05:43Z","timestamp":1787594743060,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["P30 CA168524"],"award-info":[{"award-number":["P30 CA168524"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30 AG072973"],"award-info":[{"award-number":["P30 AG072973"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R00AG050490"],"award-info":[{"award-number":["R00AG050490"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG081304"],"award-info":[{"award-number":["R01AG081304"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01AG062548"],"award-info":[{"award-number":["R01AG062548"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Impaired mitochondrial function is seen in Alzheimer's disease (AD), but its role is unclear. Mitochondrial DNA (mtDNA) supports bioenergetic metabolism, but it is uncertain how it might influence AD neuropathology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We used cytoplasmic hybrid (cybrid) cell lines made from SH\u2010SY5Y cells expressing mtDNA from cognitively healthy (CH), mild cognitive impairment (MCI), or AD individuals to investigate the impact of mtDNA\u2010determined mitochondrial function on amyloid, tau, and neurodegeneration (ATN) markers. Cybrid measurements were correlated with cognition and brain morphometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Relative to cybrids expressing mtDNA from CH individuals, MCI and AD cybrids contained more phosphorylated tau\u2010217 (p\u2010tau217), p\u2010tau181, and total tau. Cybrid p\u2010tau217 correlated with plasma p\u2010tau217 from the mtDNA donor (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.605,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.001). We observed negative relationships between cybrid p\u2010tau217 and cognition and brain morphometry. MCI and AD cybrid proteomes showed mitochondrial dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>mtDNA\u2010determined mitochondrial function affects cell physiology in AD\u2010relevant ways. Our study suggests that mtDNA affects ATN status and clinical state.<\/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>Mitochondrial DNA (mtDNA)\u2013determined mitochondrial function drives Alzheimer's disease (AD) hallmarks.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Cytoplasmic hybrid outcomes associate with mtDNA\u2010donor clinical measures.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Proteomic analyses indicate mitochondrial dysfunction in AD.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n     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Kansas USA"},{"name":"Department of Neurology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary","family":"Clark","sequence":"additional","affiliation":[{"name":"The Mass Spectrometry and Proteomics Core University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaella","family":"Rekowski","sequence":"additional","affiliation":[{"name":"The Mass Spectrometry and Proteomics Core University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Cancer Biology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"Weidling","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"Mayfield","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey S.","family":"John","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Burns","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"},{"name":"Department of Neurology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather M.","family":"Wilkins","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"},{"name":"Department of Neurology University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Biochemistry and Molecular Biology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Swerdlow","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"},{"name":"Department of Neurology University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Biochemistry and Molecular Biology University of Kansas Medical Center  Kansas City Kansas USA"},{"name":"Department of Cell Biology and Physiology University of Kansas Medical Center  Kansas City Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jill K.","family":"Morris","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center  Fairway Kansas USA"},{"name":"Department of Neurology University 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