{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:41:50Z","timestamp":1792496510472,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["101080329"],"award-info":[{"award-number":["101080329"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG072973"],"award-info":[{"award-number":["P30AG072973"]}],"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;amp; Dementia"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Diabetes is a major risk factor for Alzheimer's disease (AD), and both diseases involve mitochondrial dysfunction. Changes in mitochondrial DNA (mtDNA) can influence energy metabolism, cellular signaling, and epigenetic programming, thereby affecting cellular health. We hypothesized that AD is associated with reduced mtDNA copy number (mtDNA\u2010CN) in vulnerable brain regions, and that diabetes modifies these changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      MtDNA\u2010CN was quantified by absolute quantitative polymerase chain reaction (qPCR) in post\u2010mortem hippocampus, amygdala, and cerebellum from cognitive controls (CCs), AD, and diabetes groups (CC+D, AD+D;\n                      <jats:italic>N<\/jats:italic>\n                      \u00a0=\u00a066\u201377).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      MtDNA\u2010CN differed by region, being highest in amygdala, intermediate in hippocampus, and lowest in cerebellum (503, 421, and 160 copies\/cell;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001). Pooled analyses showed modestly lower mtDNA\u2010CN in AD. However, inclusion of diabetes appeared to mask differences. Donors with diabetes (CC+D and AD+D combined) had higher mtDNA\u2010CN than non\u2010diabetic (CC and AD combined) in hippocampus (+37.5%;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0012), amygdala (+30.6%;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0057), and cerebellum (+48.5%;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.0002). This diabetes\u2010associated increase was also present within AD, where AD+D had higher mtDNA\u2010CN than AD in all regions. Removal of diabetic donors showed that AD was associated with a 19%\u201330% lower mtDNA\u2010CN, reaching significance in the amygdala and cerebellum after correction for multiple testing.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>We show that AD is associated with multiregional mtDNA\u2010CN loss most clearly in donors without diabetes, whereas diabetes is associated with higher mtDNA\u2010CN and can mask AD\u2010related mitochondrial changes. The functional significance of higher mtDNA\u2010CN in the diabetic brain remains unclear, but evidence that diabetes acts as an effect modifier has important implications for dementia studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71870","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T11:00:11Z","timestamp":1792494011000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Why diabetes matters in dementia studies: Failure to account for diabetes status masks regional mitochondrial DNA copy number changes in human hippocampus, amygdala, and cerebellum in Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"given":"Aakruti","family":"Kaikini","sequence":"first","affiliation":[{"name":"King's College London, Diabetes and Obesity, School of Cardiovascular Medicine and Metabolic Sciences Faculty of Life Sciences and Medicine  London England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Shi","sequence":"additional","affiliation":[{"name":"King's College London, Diabetes and Obesity, School of Cardiovascular Medicine and Metabolic Sciences Faculty of Life Sciences and Medicine  London England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Francis","sequence":"additional","affiliation":[{"name":"Dept of Clinical and Biomedical Sciences University of Exeter University of Exeter Medical School  London England"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Swerdlow","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer's Disease Research Center University of Kansas School of Medicine  Fairway Kansas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Troakes","sequence":"additional","affiliation":[{"name":"Neurodegenerative Diseases Brain Bank, Department 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