ArticlebioRxiv : the preprint server for biology2026
Why diabetes matters in dementia studies: Excluding diabetes status masks regional mitochondrial DNA copy number changes in human hippocampus, amygdala, and cerebellum in Alzheimer's disease.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionDiabetes is a major risk factor for Alzheimer's 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.
methodsPost-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.
resultsOverall, 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. DISCUSSION: 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.
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