ArticleNeurobiology of aging2016
The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.
Article in Neurobiology of aging, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- The genetic association between apolipoprotein E gene polymorphism and Parkinson disease: A meta-Analysis of 47 studies.Medicine · 2018Pooled it
- Does sex moderate health and Alzheimer's disease risk tied to early educational experiences? The reducing inequities through social and educational change follow-up in early adulthood extension study protocol.Brain, behavior, & immunity - health · 2026Article
- Review
- Introducing the SAGE study: a multimodal protocol for testing a GABAergic mechanism of age-related episodic memory impairment across the sexes.BMJ neurology open · 2026Article
- Bioenergetics and lipid metabolism in Alzheimer's disease: From cell biology to systemic health.Journal of internal medicine · 2026Review
- Consideration of sex as a biological variable over the history of the 5xFAD Alzheimer's Disease mouse model.Biology of sex differences · 2025Article
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Not your mother's hormone therapy: Highly selective estrogen receptor beta agonists as next-generation therapies for menopausal symptom relief.Hormones and behavior · 2025Review
- Cerebral amyloid angiopathy: a narrative review.Frontiers in aging neuroscience · 2025Review
- Iron-associated lipid peroxidation in Alzheimer's disease is increased in lipid rafts with decreased ferroptosis suppressors, tested by chelation in mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Sex differences in histopathological markers of cerebral amyloid angiopathy and related hemorrhage.International journal of stroke : official journal of the International Stroke Society · 2024Article
- Sex and Gender Differences in Alzheimer's Disease: Genetic, Hormonal, and Inflammation Impacts.International journal of molecular sciences · 2024Review
- Low-Density Lipoprotein Receptor-Related Protein 1 as a Potential Therapeutic Target in Alzheimer's Disease.Pharmaceutics · 2024Review
- Apolipoprotein E polymorphisms and female fertility in a transgenic mouse model of Alzheimer's disease.Scientific reports · 2024Article
- Vivaria housing conditions expose sex differences in brain oxidation, microglial activation, and immune system states in aged hAPOE4 mice.Experimental brain research · 2024Article
- The novel estrogen receptor beta agonist EGX358 andFrontiers in aging neuroscience · 2024Article
- Cerebral microbleeds in patients with COVID-19: is there an inevitable connection?Brain communications · 2024Review
- Article
- Sex and interferon gamma signaling regulate microglia migration in the adult mouse cortex in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Moving beyond amyloid and tau to capture the biological heterogeneity of Alzheimer's disease.Trends in neurosciences · 2023Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS). Sex-APOE interactions were further analyzed in EFAD mice carrying human APOE alleles and familial AD genes (5XFAD (+/-) /human APOE(+/+)). At 7 months, E4FAD mice had cerebral cortex microbleeds with female excess, in contrast to humans. Cerebral amyloid angiopathy, plaques, and soluble Aβ also showed female excess. Both the cerebral microbleeds and cerebral amyloid angiopathy increased in proportion to individual Aβ load. In humans, the opposite sex bias of APOE4 allele for microbleeds versus the plaques and tangles is the first example of organ-specific, sex-linked APOE allele effects, and further shows AD as a uniquely human condition.
Indexed as
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.