ArticleProceedings of the National Academy of Sciences of the United States of America2001
Introduction of human apolipoprotein E4 "domain interaction" into mouse apolipoprotein E.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis 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
108 citing papers in PubMed, 1 synthesis or guideline pooled it, 192 citations in OpenAlex.
- ApoE4 associated with severe COVID-19 outcomes via downregulation of ACE2 and imbalanced RAS pathway.Journal of translational medicine · 2023Pooled it
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Trial
- Investigating the Causal Links between the Aging Process and Alzheimer's Disease Pathogenesis.International journal of stem cells · 2026Review
- Apolipoprotein E4 in Alzheimer's Disease: Role in Pathology, Lipid Metabolism, and Drug Treatment.International journal of molecular sciences · 2026Review
- A scalable two-step genome editing strategy for generating full-length gene-humanized mice at diverse genomic loci.Nature communications · 2026Article
- The Christchurch point mutation in mouse APOE reduces Aβ-induced tau and α-synuclein pathologies.bioRxiv : the preprint server for biology · 2025Article
- Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.Aging cell · 2025Article
- Apolipoprotein E in Alzheimer's Disease: Focus on Synaptic Function and Therapeutic Strategy.Molecular neurobiology · 2025Review
- Multi-functional role of apolipoprotein E in neurodegenerative diseases.Frontiers in aging neuroscience · 2025Review
- Article
- SR-B1-/-ApoE-R61h/h Mice Mimic Human Coronary Heart Disease.Cardiovascular drugs and therapy · 2024Review
- Circulating apoE4 protein levels from dried blood spots predict cognitive function in a large population-based survey setting.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Multifaceted roles of APOE in Alzheimer disease.Nature reviews. Neurology · 2024Review
- Apolipoprotein E polymorphisms and female fertility in a transgenic mouse model of Alzheimer's disease.Scientific reports · 2024Article
- Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.bioRxiv : the preprint server for biology · 2024Article
- Temporal Characterization of the Amyloidogenic APPswe/PS1dE9;hAPOE4 Mouse Model of Alzheimer's Disease.International journal of molecular sciences · 2024Article
- Role of Apolipoprotein E in the Hippocampus and Its Impact following Ionizing Radiation Exposure.Cells · 2024Article
- ApoE expression in macrophages communicates immunometabolic signaling that controls hyperlipidemia-driven hematopoiesis & inflammation via extracellular vesicles.Journal of extracellular vesicles · 2023Article
- Interactions of amyloidogenic proteins with mitochondrial protein import machinery in aging-related neurodegenerative diseases.Frontiers in physiology · 2023Review
- Neuronal ApoE4 in Alzheimer's disease and potential therapeutic targets.Frontiers in aging neuroscience · 2023Review
48 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Human apolipoprotein E4 (apoE4) binds preferentially to lower density lipoproteins, including very low density lipoproteins, and is associated with increased risk of atherosclerosis and neurodegenerative disorders, including Alzheimer's disease. This binding preference is the result of the presence of Arg-112, which causes Arg-61 in the amino-terminal domain to interact with Glu-255 in the carboxyl-terminal domain. ApoE2 and apoE3, which have Cys-112, bind preferentially to high density lipoproteins (HDL) and do not display apoE4 domain interaction. Mouse apoE, like apoE4, contains the equivalent of Arg-112 and Glu-255, but lacks the critical Arg-61 equivalent (it contains Thr-61). Thus, mouse apoE does not display apoE4 domain interaction and, as a result, behaves like human apoE3, including preferential binding to HDL. To assess the potential role of apoE4 domain interaction in atherosclerosis and neurodegeneration, we sought to introduce apoE4 domain interaction into mouse apoE. Replacing Thr-61 in mouse apoE with arginine converted the binding preference from HDL to very low density lipoproteins in vitro, suggesting that apoE4 domain interaction could be introduced into mouse apoE in vivo. Using gene targeting in embryonic stem cells, we created mice expressing Arg-61 apoE. Heterozygous Arg-61/wild-type apoE mice displayed two phenotypes found in human apoE4/E3 heterozygotes: preferential binding to lower density lipoproteins and reduced abundance of Arg-61 apoE in the plasma, reflecting its more rapid catabolism. These findings demonstrate the successful introduction of apoE4 domain interaction into mouse apoE in vivo. The Arg-61 apoE mouse model will allow the effects of apoE4 domain interaction in lipoprotein metabolism, atherosclerosis, and neurodegeneration to be determined.
Indexed as
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.