ReviewThe Lancet. Neurology2021
APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches.
Review in The Lancet. Neurology, 2021. 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 622 papers, 6 of them syntheses 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
622 citing papers in PubMed, 6 syntheses or guidelines pooled it, 933 citations in OpenAlex.
- Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Pooled it
- APOE in subjective cognitive decline: a systematic review and meta-analysis.Journal of neurology · 2026Pooled it
- Apolipoprotein E Alleles Across the Spectrum of Frontotemporal Lobar Degeneration: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2026Pooled it
- Cross-ancestry genome-wide association studies of liver function biomarkers uncover pleiotropic variants, systemic disease links and therapeutic targets.Genome medicine · 2026Pooled it
- Dissecting the genetic and proteomic risk factors for delirium.Nature aging · 2026Pooled it
- Clinical Practice Recommendations of the Swiss Society for Neuroradiology: Neuroimaging Standards for Enrollment and Disease Monitoring in Anti-Amyloid Immunotherapies.Neuro-degenerative diseases · 2026Guideline
- Baseline predictors of neurophysiological response to combined physical and cognitive training in older adults with subjective cognitive decline.BMC geriatrics · 2026Trial
- Exosomes in brain diseases: Mechanisms, advances, and perspectives.Bioactive materials · 2027Review
- A genome-wide association study of cognitive impairment in a Chinese cohort of 1,040 individuals.Human genetics · 2026Article
- Docosahexaenoic acid remodels lipid composition of lipid rafts and mitochondrial function in ApoE4/4 mouse brain: a multi-omic investigation.Molecular biomedicine · 2026Article
- Global and regional amyloid-β in explaining APOE-ε4 and sex associations with medial temporal tau: a neuropathology study.Acta neuropathologica · 2026Article
- Observational
- Cortical thickness signature of early-onset Alzheimer's disease across clinical stages and A/T1 biomarker profiles.Journal of neurology · 2026Article
- Exploratory Analysis of APOE ε4-Stratified Associations Between Plasma Alzheimer's Biomarkers and Retinal Imaging Metrics in Cognitively Normal Adults.Translational vision science & technology · 2026Article
- Unveiling the pathogenesis and therapeutic strategies of Alzheimer's disease through cuproptosis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026Review
- Lipid metabolism in moyamoya disease: Emerging evidence, vascular remodeling, and therapeutic implications.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- CRP-albumin-lymphocyte index and multisystem diseases: a phenome-wide Mendelian randomization study.Molecular genetics and genomics : MGG · 2026Article
- Long Non-Coding RNA PART1 in Alzheimer's Disease: Clinical Value and Improvement of Neurotoxicity and Apoptosis via miR-770-5p.Neurochemical research · 2026Article
- Association of apolipoprotein E gene with risk, cognition, and prognosis of epilepsy.Human genetics · 2026Article
- From Dysbiosis to Blood-Brain Barrier Disruption: The Metabolite-Mediated Gut-Brain Axis in Alzheimer's Disease.Molecular neurobiology · 2026Review
562 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The APOE ε4 allele remains the strongest genetic risk factor for sporadic Alzheimer's disease and the APOE ε2 allele the strongest genetic protective factor after multiple large scale genome-wide association studies and genome-wide association meta-analyses. However, no therapies directed at APOE are currently available. Although initial studies causally linked APOE with amyloid-β peptide aggregation and clearance, over the past 5 years our understanding of APOE pathogenesis has expanded beyond amyloid-β peptide-centric mechanisms to tau neurofibrillary degeneration, microglia and astrocyte responses, and blood-brain barrier disruption. Because all these pathological processes can potentially contribute to cognitive impairment, it is important to use this new knowledge to develop therapies directed at APOE. Several therapeutic approaches have been successful in mouse models expressing human APOE alleles, including increasing or reducing APOE levels, enhancing its lipidation, blocking the interactions between APOE and amyloid-β peptide, and genetically switching APOE4 to APOE3 or APOE2 isoforms, but translation to human clinical trials has proven challenging.
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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.