ReviewFrontiers in aging neuroscience2018
Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer's Disease.
Review in Frontiers in aging neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 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
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.
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- Systematic review and meta-analysis of the effects of menopause hormone therapy on risk of Alzheimer's disease and dementia.Frontiers in aging neuroscience · 2023Pooled it
- Article
- Migraine and menopause as converging factors in brain vulnerability: a hypothesis-driven perspective.The journal of headache and pain · 2026Review
- Meta analysis of glucose metabolism across Alzheimer's, Parkinson's and ALS Reveals emergence of adaptive brain glucometabolic responses and associated neurological functional profiles.medRxiv : the preprint server for health sciences · 2026Article
- APOE4 Accelerates Menopause-Associated Brain Metabolic Shift and Disrupts Bioenergetic Adaptation.bioRxiv : the preprint server for biology · 2026Article
- The APOE4-estrogen-microglia axis in perimenopausal cognitive changes: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- APOE4 accelerates menopause-associated brain metabolic shift and disrupts bioenergetic adaptation.Frontiers in aging neuroscience · 2026Article
- Proteomic landscape of multidimensional aging phenotypes.Genome medicine · 2025Article
- A Case for estradiol: younger brains in women with earlier menarche and later menopause.GigaScience · 2025Article
- Machine learning-assisted network pharmacology reveals that the Chaihu-Longgu-Muli decoction modulates the inflammatory microenvironment to treat perimenopausal syndrome.Frontiers in molecular biosciences · 2025Article
- Accelerated midlife endocrine and bioenergetic brain aging in APOE4 females.Frontiers in aging neuroscience · 2025Article
- Effects of high fat diet on metabolic health vary by age of menopause onset.International journal of obesity (2005) · 2024Article
- Sex difference in human diseases: mechanistic insights and clinical implications.Signal transduction and targeted therapy · 2024Review
- The Effects of Rice Bran on Neuroinflammation and Gut Microbiota in Ovariectomized Mice Fed a Drink with Fructose.Nutrients · 2024Article
- Menopause-Associated Depression: Impact of Oxidative Stress and Neuroinflammation on the Central Nervous System-A Review.Biomedicines · 2024Review
- The association between testosterone and serum soluble klotho in the females: evidence from the NHANES database.Frontiers in endocrinology · 2024Article
- A review and analysis of key biomarkers in Alzheimer's disease.Frontiers in neuroscience · 2024Review
- A case for seeking sex-specific treatments in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- The X factor in neurodegeneration.The Journal of experimental medicine · 2022Article
- Evidence of emerging BBB changes in mid-age apolipoprotein E epsilon-4 carriers.Brain and behavior · 2022Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Neuro-inflammatory processes that contribute to development of Alzheimer's are evident early in the latent prodromal phase and worsen during the course of the disease. Despite substantial mechanistic and clinical evidence of inflammation, therapeutic approaches targeting inflammation have failed to alter the course of the disease. Disparate results from epidemiological and clinical trials targeting inflammation, highlight the complexity of the inflammatory process. Herein we review the dynamics of the inflammatory process across aging, midlife endocrine transitions, and the APOEε4 genotype and their contribution to progression of Alzheimer's disease (AD). We discuss the chronic inflammatory processes that are activated during midlife chronological and endocrine aging, which ultimately limit the clearance capacity of microglia and lead to immune senescence. Aging, menopause, and APOEε4 combine the three hits of a compromised bioenergetic system of menopause with the chronic low grade innate inflammation of aging with the APOEε4 dyslipidemia and adaptive immune response. The inflammatory immune response is the unifying factor that bridges across each of the risk factors for AD. Immune system regulators that are specific to stage of disease and inflammatory phenotype would provide a therapeutic strategy to disconnect the bridge that drives disease. Outcomes of this analysis provide plausible mechanisms underlying failed clinical trials of anti-inflammatory agents in Alzheimer's patients. Further, they highlight the need for stratifying AD clinical trial cohorts based on inflammatory phenotype. Combination therapies that include targeted use of anti-inflammatory agent's specific to the immune phenotype are considered.
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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.