ArticlePloS one2020
Redefining transcriptional regulation of the APOE gene and its association with Alzheimer's disease.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 49 citations in OpenAlex.
- Exploring the associations between lifestyle and dietary patterns with preclinical alzheimer's disease: findings from La Rioja cohort study.European journal of nutrition · 2026Article
- Apolipoprotein E drives microglia activation in the development of autoimmune uveitis through up-regulation of peptidyl prolyl isomerase F.Science advances · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Human cytomegalovirus induces neuronal gene expression through IE1 for viral maturation.Nature communications · 2025Article
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- Epigenetic and genetic risk of Alzheimer disease from autopsied brains in two ethnic groups.Acta neuropathologica · 2024Article
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- Association of TMEM106B with CorticalGenes · 2024Article
- A familial missense variant in the Alzheimer's disease gene SORL1 impairs its maturation and endosomal sorting.Acta neuropathologica · 2024Article
- The Impact of Apolipoprotein E (Biology · 2023Review
- Alternative splicing events as peripheral biomarkers for motor learning deficit caused by adverse prenatal environments.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- A familial missense variant in the Alzheimer's Disease genebioRxiv : the preprint server for biology · 2023Article
- Diet, sex, and genetic predisposition to obesity and type 2 diabetes modulate motor and anxiety-related behaviors in mice, and alter cerebellar gene expression.Behavioural brain research · 2023Article
- circRNA fromInternational journal of molecular sciences · 2023Article
- MeCP2 Is an Epigenetic Factor That Links DNA Methylation with Brain Metabolism.International journal of molecular sciences · 2023Review
- Review
- The Role of Epigenetics in Neuroinflammatory-Driven Diseases.International journal of molecular sciences · 2022Review
- A Review of the Recent Advances in Alzheimer's Disease Research and the Utilization of Network Biology Approaches for Prioritizing Diagnostics and Therapeutics.Diagnostics (Basel, Switzerland) · 2022Review
- Profile ofInternational journal of molecular sciences · 2022Article
- ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease.Neurobiology of aging · 2022Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The apolipoprotein E gene (APOE) is the strongest genetic risk factor for late-onset Alzheimer's disease (AD), yet the expression of APOE is not clearly understood. For example, it is unclear whether AD patients have elevated or decreased APOE expression or why the correlation levels of APOE RNA and the ApoE protein differ across studies. Likewise, APOE has a single CpG island (CGI) that overlaps with its 3'-exon, and this CGI's effect is unknown. We previously reported that the APOE CGI is highly methylated in human postmortem brain (PMB) and that this methylation is altered in AD frontal lobe. In this study, we comprehensively characterized APOE RNA transcripts and correlated levels of RNA expression with DNA methylation levels across the APOE CGI. We discovered the presence of APOE circular RNA (circRNA) and found that circRNA and full-length mRNA each constitute approximately one third of the total APOE RNA, with truncated mRNAs likely constituting some of the missing fraction. All APOE RNA species demonstrated significantly higher expression in AD frontal lobe than in control frontal lobe. Furthermore, we observed a negative correlation between the levels of total APOE RNA and DNA methylation at the APOE CGI in the frontal lobe. When stratified by disease status, this correlation was strengthened in controls but not in AD. Our findings suggest a possible modified mechanism of gene action for APOE in AD that involves not only the protein isoforms but also an epigenetically regulated transcriptional program driven by DNA methylation in the APOE CGI.
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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 OpenQuestion graph.