ArticleFrontiers in aging neuroscience2025
Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females.
Article in Frontiers in aging neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed.
- Dietary phytoestrogen ameliorates ovarian toxicant-induced neurotoxicity: mechanistic and metabolic insights.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Sex differences in brain glucose metabolism and Alzheimer's disease risk and progression.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Addition of humanized APP to humanizedbioRxiv : the preprint server for biology · 2026Article
- Alzheimer's Disease Risk Factor APOE4 Exerts Dimorphic Effects on Female Bone.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- Sex and APOE genotype specific brain regional vulnerability to Alzheimer's Disease.GeroScience · 2026Article
- Humanized APOE mouse brain volume increases over age irrespective of sex and APOE genotype: implications for translational validity to the human.Frontiers in neuroscience · 2026Article
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
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Authors and funding
7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Female sex, age, and APOE4 genotype are the greatest risk factors for Alzheimer's disease. Using a translational perimenopause mouse model based on human Stages of Reproductive Aging Works (STRAW) criteria, we investigated the impact of APOE genotype on female midlife endocrine aging, peripheral metabolic indicators, brain bioenergetic pathways, mitochondrial function, neuroimmune activation, and myelination. Compared to APOE3 females, APOE4 females exhibited accelerated endocrine aging that was coincident with failure to mount adaptive bioenergetic reprogramming and significant decline in mitochondrial function that were coupled with increased immune activation and demyelination in brain. In women, APOE4 was associated with early menopause. Further, APOE4 women experiencing early menopause exhibited the highest risk of Alzheimer's. These results provide plausible mechanistic pathways underlying the earlier emergence and greater risk of Alzheimer's in APOE4 postmenopausal females. Collectively, these findings support midlife as a critical window for intervention to prevent or delay the onset of the prodromal stage of Alzheimer's disease in APOE4 carriers.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.