Faculty, Staff and Student Publications
Language
English
Publication Date
1-1-2026
Journal
Frontiers in Aging Neuroscience
DOI
10.3389/fnagi.2026.1761702
PMID
41952873
PMCID
PMC13055547
PubMedCentral® Posted Date
3-14-2026
PubMedCentral® Full Text Version
Post-print
Abstract
Alzheimer's disease (AD), the most common form of dementia, accounts for 70% of cases and remains a major healthcare challenge due to its rising prevalence and lack of disease-modifying treatments. Clinically, AD is a sexually dimorphic disease. Women exhibit more rapid cognitive decline and accelerated brain atrophy during mild cognitive impairment and early dementia, whereas men more frequently present cardiovascular comorbidities, earlier mitochondrial dysfunction, and greater neuropsychiatric symptoms. AD is marked by amyloid-β (Aβ) plaques, neurofibrillary tangles, neuroinflammation, and neuronal loss, with mitochondrial dysfunction emerging as a key early contributor that exhibits sex specific phenotypes. Mitochondria are vital for neuronal function by generating ATP, maintaining calcium homeostasis, and regulating oxidative stress. However, mitochondria in AD exhibit impaired ATP synthesis, excessive reactive oxygen species (ROS) production, calcium dysregulation, and disrupted fission-fusion dynamics. AD mitochondrial dysfunction can be measured by molecular markers, such as increased expression of fission-related protein Drp1, decreased biogenesis regulator PGC-1α, and elevated oxidative stress markers like malonaldehyde, nitotyrosine and protein carbonyls. Accumulating data suggest that sex differences in mitochondrial dysfunction are attributed to either sex hormonal or sex chromosomal effects, which eventually contribute to sex dichotomic phenotypes of AD. This review collected data regarding mitochondrial dysfunction in AD, with an emphasis on sex differences in oxidative stress, energy metabolism, and regulatory pathways.
Keywords
Alzheimer's disease, dementia, mitochondria, oxidative stress, sex differences
Published Open-Access
yes
Recommended Citation
Afzal Misrani, Conelius Ngwa, and Fudong Liu, "Mitochondrial Dysfunction in Alzheimer’s Disease and Related Sex Differences" (2026). Faculty, Staff and Student Publications. 3788.
https://digitalcommons.library.tmc.edu/uthmed_docs/3788