ArticleInternational journal of Alzheimer's disease2011
The apolipoprotein e antagonistic pleiotropy hypothesis: review and recommendations.
Article in International journal of Alzheimer's disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03461861 (Network-Level Mechanisms for Preclinical Alzheimer's Disease Development), which is not on this map. Cited by 100 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.
Network-Level Mechanisms for Preclinical Alzheimer's Disease Development
Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Meta-analysis of cognitive ability differences by apolipoprotein e genotype in young humans.Neuroscience and biobehavioral reviews · 2018Pooled it
- Influence of APOE genotype on whole-brain functional networks in cognitively normal elderly.PloS one · 2013Trial
- Shared genetic and molecular architecture between insulin resistance and cognitive performance.medRxiv : the preprint server for health sciences · 2026Article
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- The Human Pleiotropic Map of GWAS Associations and Therapeutic Implications.bioRxiv : the preprint server for biology · 2026Article
- APOE ε4 and Accelerated Cognitive Decline Among Cognitively Healthy Middle-Aged and Older Adults.JAMA network open · 2026Article
- The effect of Apolipoprotein E4 on cognitive function in Parkinson's disease: A structural MRI study in the PPMI cohort.PloS one · 2026Article
- Amyloid-Frontiers in aging neuroscience · 2026Article
- APOE-ε4 moderates the association between diet quality and executive function in middle-aged women at increased risk for Alzheimer's disease.Journal of nutritional science · 2026Article
- Genetic and functional evidence implicates amedRxiv : the preprint server for health sciences · 2025Article
- APOE ε4-related differences in brain structure, function, and connectivity at midlife: A scoping review.The journal of prevention of Alzheimer's disease · 2025Article
- Sex andInternational journal of molecular sciences · 2025Article
- Article
- Advancements in the investigation of the mechanisms underlying cognitive aging.Biogerontology · 2025Review
- APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.Nature medicine · 2025Article
- Article
- Impact ofProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sex differences in APOE- and PICALM-related cognitive profiles in healthy middle-aged adults.Frontiers in aging · 2025Article
- Apolipoprotein E epsilon4 allele is associated with better performance language and visual memory in spinocerebellar ataxia type 3.European journal of neurology · 2025Article
- APOE ɛ4 and Insulin Resistance Influence Path-Integration-Based Navigation through Distinct Large-Scale Network Mechanisms.Aging and disease · 2024Article
40 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
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Research on apolipoprotein E (APOE) has consistently revealed a relationship between the gene's ε4 allele and risk for development of Alzheimer's disease (AD). However, research with younger populations of ε4 carriers has suggested that the APOE ε4 allele may in fact be beneficial in earlier ages and may only confer risk of cognitive decline later in life. Accordingly, we and others have proposed that APOE may represent an example of antagonistic pleiotropy. Antagonistic pleiotropy is an evolutionary biology concept that proposes certain genes or alleles that may differentially impact fitness during different life stages. We critically review this hypothesis in light of new research of the impact of APOE on cognition and neural integrity across the lifespan. We provide recommendations for the revision of the antagonistic pleiotropy hypothesis of APOE and suggest important avenues for future research in this area.
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.