ArticleCommunications medicine2025
Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.
Article in Communications medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
4 citing papers in PubMed.
- VCD-induced estropause fails to enhance responsiveness to 17α-estradiol in adult female mice.GeroScience · 2026Article
- 17α-Estradiol: A mildly feminizing estrogen with sex-specific metabolic and lifespan benefits.Ageing research reviews · 2026Review
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- APOE genotype confers context-dependent neurovascular vulnerability in immune-vascularized human forebrain organoids.bioRxiv : the preprint server for biology · 2025Article
Corrections and comments
- Update of
Authors and funding
10 authors.
Funding
Abstract
backgroundThe apolipoprotein ε4 allele (APOE4) is associated with decreased longevity and increased vulnerability to age-related declines and disorders across multiple systems. Interventions that promote healthspan and lifespan represent a promising strategy to attenuate the development of APOE4-associated aging phenotypes. Here, we studied the ability of the longevity-promoting intervention 17α-estradiol (17αE2) to protect against impairments in APOE4 versus the predominant APOE3 genotype using early middle-aged mice with knock-in of human APOE alleles.
methodsBeginning at age 10 months, male APOE3 or APOE4 mice were treated for 20 weeks with 17αE2 or vehicle then compared body-wide for indices of middle-aged phenotypes.
resultsAcross peripheral and neural measures, APOE4 associates with poorer outcomes. Notably, 17αE2 treatment generally improves outcomes in a genotype-dependent manner, favoring APOE4 mice, including reductions in body weight, plasma leptin, hepatic steatosis, learning and memory, and oxidative damage in the brain. Plasma lipidomics and microglial transcriptomics show reductions in genotype-specific differences with 17αE2 treatment.
conclusionsThese findings demonstrate that APOE4 promotes systemic and neural aging phenotypes linked to AD and that 17αE2-mediated healthspan actions show a positive APOE4 bias. Collectively, the findings suggest that longevity-promoting interventions may be useful in mitigating deleterious age-related risks associated with the APOE4 genotype.
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.