{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T18:42:18Z","timestamp":1785436938737,"version":"3.56.0"},"posted":{"date-parts":[[2026,6,8]]},"group-title":"Neuroscience","reference-count":40,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T00:00:00Z","timestamp":1780876800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"crossref","award":["Interdisciplinary Research Grant ARUK-IRG2020A-001"],"award-info":[{"award-number":["Interdisciplinary Research Grant ARUK-IRG2020A-001"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"crossref","award":["101080329"],"award-info":[{"award-number":["101080329"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"crossref"}]},{"award":["P30AG072973"],"award-info":[{"award-number":["P30AG072973"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,8]]},"abstract":"<jats:title>STRUCTURED ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>INTRODUCTION<\/jats:title>\n                  <jats:p>Diabetes is a major risk factor for Alzheimer\u2019s disease (AD), and both diseases involve mitochondrial dysfunction. We hypothesised that AD is associated with reduced mitochondrial DNA copy number (mtDNA-CN) 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>Post-mortem hippocampus, amygdala, and cerebellum samples (N=66-77) from non-cognitively impaired (NCI) and AD donors, with and without diabetes, were analysed. mtDNA-CN was quantified by absolute quantification.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Overall, mtDNA-CN was lower in AD. However, stratification by diabetes revealed opposite changes: non-diabetic AD cases showed reduced mtDNA-CN, whereas diabetic cases showed higher mtDNA-CN across all regions irrespective of cognitive status.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>These findings confirm multiregional loss of mtDNA-CN in the AD brain, most evident in the absence of diabetes. The functional significance of higher mtDNA-CN in the diabetic brain remains unclear, but evidence that diabetes can mask effects has important implications for dementia studies.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.03.729204","type":"posted-content","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T08:50:16Z","timestamp":1780908616000},"source":"Crossref","is-referenced-by-count":0,"title":["Why diabetes matters in dementia studies: Excluding diabetes status masks regional mitochondrial DNA copy number changes in human hippocampus, amygdala, and cerebellum in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"given":"Aakruti","family":"Kaikini","sequence":"first","affiliation":[{"name":"King\u2019s College London, Diabetes and Obesity, School of Cardiovascular Medicine and Metabolic Sciences, Faculty of Life Sciences and Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anqi","family":"Shi","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Diabetes and Obesity, School of Cardiovascular Medicine and Metabolic Sciences, Faculty of Life Sciences and Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Francis","sequence":"additional","affiliation":[{"name":"University of Exeter, Dept of Clinical and Biomedical Sciences, University of Exeter Medical School, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russell","family":"Swerdlow","sequence":"additional","affiliation":[{"name":"University of Kansas Alzheimer\u2019s Disease Research Center, University of Kansas School of Medicine, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Troakes","sequence":"additional","affiliation":[{"name":"King\u2019s College London, London Neurodegenerative Diseases Brain Bank, Department of Clinical and Basic Neuroscience, Institute of Psychiatry, Psychology &Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0414-0758","authenticated-orcid":false,"given":"Jaimee","family":"Kennedy","sequence":"additional","affiliation":[{"name":"King\u2019s College London, London Neurodegenerative Diseases Brain Bank, Department of Clinical and Basic Neuroscience, Institute of Psychiatry, Psychology &Neuroscience"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1636-491X","authenticated-orcid":false,"given":"Alan","family":"Hodgkinson","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Department of Medical and Molecular Genetics, School of Basic and Medical Biosciences."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7207-1666","authenticated-orcid":false,"given":"Afshan N.","family":"Malik","sequence":"additional","affiliation":[{"name":"King\u2019s College London, Diabetes and Obesity, School of Cardiovascular Medicine and Metabolic Sciences, Faculty of Life Sciences and Medicine."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061007302294000_2026.06.03.729204v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00249-8"},{"key":"2026061007302294000_2026.06.03.729204v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/S13311-022-01185-Z"},{"key":"2026061007302294000_2026.06.03.729204v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01296-0"},{"key":"2026061007302294000_2026.06.03.729204v1.4","unstructured":"International Diabetes Federation. 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