Journal Article Preprint Epublish
PubMed: 42327071 DOI: 10.64898/2026.06.03.729204
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.
bioRxiv
Authors: Aakruti Kaikini, Anqi Shi, Paul Francis, Russell Swerdlow, Claire Troakes, Jaimee Kennedy, Alan Hodgkinson, Afshan N Malik
Abstract
INTRODUCTION
Diabetes 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.
METHODS
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.
RESULTS
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.
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.
MeSH
Diabetes Mellitus, Hippocampus, Dementia, Alzheimer Disease, Brain, Masks, Amygdala, Cerebellum, Dna, Mitochondrial, Dna