SynthesisJournal of translational medicine2023
ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.
Synthesis in Journal of translational medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 32 citations in OpenAlex.
- Lack of association between APOE genotypes and COVID-19 in a black South African cohort.Scientific reports · 2026Article
- Intersection of COVID-19 and Alzheimer's Disease: Genetic Insights and Neuropathological Consequences.Biochemical genetics · 2026Review
- Integrating Host Genetics and Clinical Setting in Machine Learning Models: Predicting COVID-19 Prognosis for Healthcare Decision-Making (The FeMiNa Study).Diagnostics (Basel, Switzerland) · 2026Article
- ACE2: Friend or Foe in Post-COVID-19 Neurodegeneration?International journal of molecular sciences · 2025Review
- KGG: a fully automated workflow for creating disease-specific knowledge graphs.Bioinformatics (Oxford, England) · 2025Article
- Infections withFrontiers in aging neuroscience · 2025Review
- Comparative analysis of dynamic transcriptomes reveals specific COVID-19 features and pathogenesis of immunocompromised populations.mSystems · 2024Article
- APOE2 protects against Aβ pathology by improving neuronal mitochondrial function through ERRα signaling.Cellular & molecular biology letters · 2024Article
- Risk factors for severe COVID-19 disease increase SARS-CoV-2 infectivity of endothelial cells and pericytes.Open biology · 2024Article
- Molecular cross-talk between long COVID-19 and Alzheimer's disease.GeroScience · 2024Review
- DoFrontiers in nutrition · 2024Article
- Exploring the viability of Zeatin as a prospective therapeutic candidate for investigating the complex interplay between severe acute respiratory syndrome coronavirus (SARS-CoV) and Alzheimer's disease.In silico pharmacology · 2024Article
- Post-COVID-19 Cognitive Decline and Apoe Polymorphism: Towards a Possible Link?Brain sciences · 2023Article
- Review
- Analysis of Potential Biomarkers in Frontal Temporal Dementia: A Bioinformatics Approach.International journal of molecular sciences · 2023Article
- Apolipoprotein E and viral infection: Risks and Mechanisms.Molecular therapy. Nucleic acids · 2023Review
- Blood ACE2 Protein Level Correlates with COVID-19 Severity.International journal of molecular sciences · 2023Article
- Article
- Review
- Sister haplotypes and recombination disequilibrium: a new approach to identify associations of haplotypes with complex diseases.Frontiers in genetics · 2023Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent numerous epidemiology and clinical association studies reported that ApoE polymorphism might be associated with the risk and severity of coronavirus disease 2019 (COVID-19), and yielded inconsistent results. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) receptor expressed on host cell membranes.
methodsA meta-analysis was conducted to clarify the association between ApoE polymorphism and the risk and severity of COVID-19. Multiple protein interaction assays were utilized to investigate the potential molecular link between ApoE and the SARS-CoV-2 primary receptor ACE2, ApoE and spike protein. Immunoblotting and immunofluorescence staining methods were used to access the regulatory effect of different ApoE isoform on ACE2 protein expression.
resultsApoE gene polymorphism (ε4 carrier genotypes VS non-ε4 carrier genotypes) is associated with the increased risk (P = 0.0003, OR = 1.44, 95% CI 1.18-1.76) and progression (P < 0.00001, OR = 1.85, 95% CI 1.50-2.28) of COVID-19. ApoE interacts with both ACE2 and the spike protein but did not show isoform-dependent binding effects. ApoE4 significantly downregulates ACE2 protein expression in vitro and in vivo and subsequently decreases the conversion of Ang II to Ang 1-7.
conclusionsApoE4 increases SARS-CoV-2 infectivity in a manner that may not depend on differential interactions with the spike protein or ACE2. Instead, ApoE4 downregulates ACE2 protein expression and subsequently the dysregulation of renin-angiotensin system (RAS) may provide explanation by which ApoE4 exacerbates COVID-19 disease.
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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 Socratic graph.