ArticleNature medicine2024
APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease.
Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 247 papers, 4 of them syntheses that pooled it.
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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
247 citing papers in PubMed, 4 syntheses or guidelines pooled it.
- A reappraisal of APOE genetic effects on Alzheimer's disease risk in the Japanese population: a meta-analysis.Molecular neurodegeneration · 2026Pooled it
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Herpesviruses, antiviral treatment, and the risk of dementia - systematic review and meta-analysis.Alzheimer's research & therapy · 2025Pooled it
- GWAS of CRP response to statins further supports the role of APOE in statin response: A GIST consortium study.Pharmacological research · 2025Pooled it
- Trial
- Alzheimer's blood-based biomarkers, incident dementia, and interactions with age, APOE status, and hormone therapy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Trial
- Telomere dynamics are influenced by sleep, sleep variability and circadian rhythms in older adults with or without alzheimer's risk.Alzheimer's research & therapy · 2025Trial
- Trial
- Lower baseline amyloid beta burden is associated with greater percent of amyloid beta positron emission tomography reduction and better clinical outcomes in the aducanumab Phase 3 trials ENGAGE and EMERGE in early Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Trial
- APOE4-AGE axis is linked to mtDNA release and cGAS-STING-mediated neuroinflammation in the aging brain.Free radical biology & medicine · 2026Article
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- Accelerated hippocampal atrophy in APOE ε4 homozygotes and females: Longitudinal findings from the Tohoku Medical Megabank MRI study.Neuroradiology · 2026Article
- Associations between polygenic risk for obesity, body mass index and cognitive performance: Age as moderating factor.Brain, behavior, & immunity - health · 2026Article
- Prosocial helping behaviors attenuate accelerated cognitive decline driven by APOE ε4.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Review
- Human Stem Cell-Derived Models of the Alzheimer's Disease Neuroimmune System.International journal of molecular sciences · 2026Review
- GLP-1 receptor agonists for Alzheimer's disease: Lessons from trials and translational challenges.Cell reports. Medicine · 2026Review
- Novel Plasma Proteins Associated With Alzheimer's Disease Risk in APOE ε4 Carriers and Non-carriers.Research square · 2026Article
- Proteomic signatures of protected APOE ε4 carriers reveal causal pathways associated with delayed Alzheimer's disease onset.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Genetic Associations with Temporal Modeling of Alzheimer's Disease Progression Supports a Novel Paradigm for Disease Risk.medRxiv : the preprint server for health sciences · 2026Article
187 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
This study aimed to evaluate the impact of APOE4 homozygosity on Alzheimer's disease (AD) by examining its clinical, pathological and biomarker changes to see whether APOE4 homozygotes constitute a distinct, genetically determined form of AD. Data from the National Alzheimer's Coordinating Center and five large cohorts with AD biomarkers were analyzed. The analysis included 3,297 individuals for the pathological study and 10,039 for the clinical study. Findings revealed that almost all APOE4 homozygotes exhibited AD pathology and had significantly higher levels of AD biomarkers from age 55 compared to APOE3 homozygotes. By age 65, nearly all had abnormal amyloid levels in cerebrospinal fluid, and 75% had positive amyloid scans, with the prevalence of these markers increasing with age, indicating near-full penetrance of AD biology in APOE4 homozygotes. The age of symptom onset was earlier in APOE4 homozygotes at 65.1, with a narrower 95% prediction interval than APOE3 homozygotes. The predictability of symptom onset and the sequence of biomarker changes in APOE4 homozygotes mirrored those in autosomal dominant AD and Down syndrome. However, in the dementia stage, there were no differences in amyloid or tau positron emission tomography across haplotypes, despite earlier clinical and biomarker changes. The study concludes that APOE4 homozygotes represent a genetic form of AD, suggesting the need for individualized prevention strategies, clinical trials and treatments.
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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.