ArticleNeurobiology of aging2008
The APOE4 genotype alters the response of microglia and macrophages to 17beta-estradiol.
Article in Neurobiology of aging, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
What it found
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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
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Use of Hormone Therapy in Postmenopausal Women with Alzheimer's Disease: A Systematic Review.Drugs & aging · 2021Pooled it
- Dementia risk across distinct metabolic profiles in the UK Biobank.GeroScience · 2026Article
- APOE4 negates the effects of ovarian hormones on cerebrovascular endothelial and mitochondrial function.The Journal of physiology · 2026Article
- Reproductive history differentially shapes the neural response of middle-aged hAPOEɛ4 female rats to estradiol therapy after a metabolic challenge.Biology of sex differences · 2026Article
- A ketogenic diet improves memory in females in the APOE4 mouse model of Alzheimer's disease.GeroScience · 2026Article
- Beyond Estrogen: Unraveling the Complexities of Hormonal Signaling Pathways in Alzheimer's Disease and Their Implications for Precision Therapy.Molecular neurobiology · 2025Review
- Sex differences in the mediating role of brain-derived neurotrophic factor between inflammation and memory in cirrhotic patients with minimal hepatic encephalopathy.Brain, behavior, & immunity - health · 2025Article
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Blood ammonia and eye-hand coordination negatively affect health-related quality of life in women with minimal hepatic encephalopathy.Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation · 2025Article
- Sex differences in age-associated neurological diseases-A roadmap for reliable and high-yield research.Science advances · 2025Review
- Sex Differences in Longitudinal Tau-PET in Preclinical Alzheimer Disease: A Meta-Analysis.JAMA neurology · 2025Article
- Estradiol improves behavior in FAD transgenic mice that expressFrontiers in endocrinology · 2024Article
- Effects of obesogenic diet and 17β-estradiol in female mice withFrontiers in aging neuroscience · 2024Article
- Role of estrogen in women's Alzheimer's disease risk as modified by APOE.Journal of neuroendocrinology · 2023Review
- Factors Influencing Alzheimer's Disease Risk: Whether and How They are Related to the APOE Genotype.Neuroscience bulletin · 2022Review
- Sex andBrain communications · 2022Article
- The Links between Cardiovascular Diseases and Alzheimer's Disease.Current neuropharmacology · 2021Review
- Sex-dependent effect ofDisease models & mechanisms · 2020Review
- The novel estrogenic receptor GPR30 alleviates ischemic injury by inhibiting TLR4-mediated microglial inflammation.Journal of neuroinflammation · 2018Article
- Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer's Disease.Frontiers in aging neuroscience · 2018Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The apolipoprotein E4 (APOE4) gene is a well-known risk factor for Alzheimer's disease (AD) and other neurological disorders. Post-menopausal women with AD who express at least one APOE4 gene have more severe neuropathology and worsened cognitive scores than their non-expressing counterparts. Since 17beta-estradiol down-regulates inflammation as part of its neuroprotective role, we examined the effect of 17beta-estradiol on the response of microglia to immune activation as a function of APOE genotype. Our data show that the anti-inflammatory activity of 17beta-estradiol is significantly reduced in APOE4 targeted replacement mice compared to APOE3 mice. A significant interaction between APOE genotype and the response to 17beta-estradiol was observed for NO and cytokine production by immune activated microglia. The genotype specific effect was not restricted to brain macrophages since peritoneal macrophages from APOE4 ovariectomized mice also demonstrated a significant difference in 17beta-estradiol responsiveness. ERbeta protein levels in APOE4 microglia were higher than APOE3 microglia, suggesting a difference in post-translational protein regulation in the presence of the APOE4 gene. Overall, our data indicate that the APOE genotype may be a critical component in assessing the effectiveness of 17beta-estradiol's action and may impact the neuroprotective role of 17beta-estradiol and of hormone replacement therapy on brain function when the APOE4 gene is expressed.
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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 OpenQuestion graph.