Affinage

APOE

Apolipoprotein E · UniProt P02649

Length
317 aa
Mass
36.2 kDa
Annotated
2026-06-09
100 papers in source corpus 13 papers cited in narrative 13 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ApoE is a secreted, two-domain lipid transport protein that governs cholesterol and lipoprotein trafficking in the periphery and brain, with allele-specific structural differences (ε2/ε3/ε4) translating into differential disease risk (PMID:24115173). In lipid handling, lipid-free ApoE3 binds ABCA1 directly, competes with apoA-I, and drives ABCA1-dependent cholesterol efflux to form nascent 9–15 nm prebeta HDL-sized particles (PMID:14754908), while lipidated ApoE engages the LDL receptor in an isoform-graded manner that controls neuronal cholesteryl-ester uptake; impaired LDLR binding by ApoE2 and the Christchurch mutation reduces uptake and is protective, whereas ApoE4 promotes lysosomal lipofuscinosis and retention of tau fibrils (ApoE4 > ApoE3 > ApoE2) (PMID:39532095). In Aβ metabolism, ApoE does not appreciably bind soluble Aβ directly but instead competes with Aβ for LRP1-dependent cellular uptake in astrocytes (PMID:23620513) and enhances proteolytic Aβ degradation by neprilysin and insulin-degrading enzyme in a lipidation-dependent manner stimulated by LXR activation (PMID:18549781). ApoE also acts as a high-affinity checkpoint inhibitor of the classical complement cascade by binding activated C1q (KD ~140–580 pM), suppressing complement-driven leukocyte infiltration (PMID:30692699), and ApoE3 (but not ApoE4) preserves synaptic, dendritic, and axonal integrity against excitotoxic neurodegeneration (PMID:10366621). In aged mesenchymal progenitor cells, APOE accumulation drives cellular senescence by promoting autophagy-lysosomal degradation of nuclear lamina proteins and KAP1, destabilizing heterochromatin (PMID:37117743), and APOE is transcriptionally upregulated as part of an inflammatory program downstream of mitochondrial/electron-transport-chain dysfunction (PMID:37171075). Peripherally, ApoE expression is sufficient to reverse hypercholesterolemia and atherosclerotic lesions in ApoE-deficient mice (PMID:10669641), is required for PCSK9-mediated hepatic lipogenesis (PMID:26980204), and specific coding variants alter LDLR binding affinity and contribute to dysbetalipoproteinemia (PMID:37051929).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    Established that ApoE protects against neurodegeneration in an isoform-specific manner, framing ApoE3 as neuroprotective and ApoE4 as deficient in this protection.

    Evidence Neuron-specific expression of human apoE3 or apoE4 in Apoe-/- mice with kainic acid challenge and immunohistochemical quantification of synaptic/dendritic/axonal markers

    PMID:10366621

    Open questions at the time
    • Molecular mechanism of ApoE3 neuroprotection not defined
    • Does not connect protection to a specific receptor or lipid pathway
  2. 1999 Medium

    Showed that truncated ApoE fragments are directly neurotoxic via receptor- and calcium-dependent mechanisms, implicating ApoE proteolysis in neuronal injury.

    Evidence Primary embryonic rat hippocampal neuron culture with calcium imaging and pharmacological inhibition (RAP, MK-801)

    PMID:10436064

    Open questions at the time
    • Single lab without structural or reconstitution confirmation
    • Identity of the cell-surface receptor mediating toxicity not pinned down
    • Relevance of fragment generation in vivo unclear
  3. 2000 Medium

    Demonstrated that ApoE expression is sufficient not only to correct hypercholesterolemia but to reverse pre-existing atherosclerotic lesions, establishing causal sufficiency for vascular protection.

    Evidence Adenoviral APOE gene transfer into ApoE-/- nude mice with plasma lipid and aortic lesion quantification

    PMID:10669641

    Open questions at the time
    • Single lab
    • Does not isolate which ApoE function (clearance vs efflux) drives regression
    • No isoform comparison
  4. 2004 High

    Identified ABCA1 as a direct ApoE3 binding partner mediating cholesterol efflux and biogenesis of nascent ApoE-HDL particles, linking ApoE to reverse cholesterol transport machinery.

    Evidence 125I-apoA-I competition binding, cholesterol efflux assays in ABCA1 mutant (Tangier C1477R) fibroblasts, and native PAGE particle sizing

    PMID:14754908

    Open questions at the time
    • Isoform dependence of ABCA1 binding not fully resolved
    • Structural basis of ApoE-ABCA1 interaction unknown
  5. 2008 High

    Established that ApoE facilitates proteolytic Aβ clearance in a lipidation-dependent manner, connecting ApoE lipid state and LXR signaling to amyloid degradation.

    Evidence In vitro degradation assays with microglia/purified neprilysin and IDE, plus LXR agonist treatment of Tg2576 mice with brain Aβ and memory readouts

    PMID:18549781

    Open questions at the time
    • Quantitative isoform contributions to clearance not separated
    • Whether effect is direct enzyme modulation or substrate presentation unclear
  6. 2013 High

    Resolved the mechanism of ApoE-Aβ interaction by showing ApoE does not bind soluble Aβ directly but competes for LRP1-mediated uptake, reframing ApoE as a clearance modulator rather than an Aβ chaperone.

    Evidence SEC, native PAGE, SPR biochemistry plus in vivo brain Aβ microdialysis and astrocyte LRP1 competition assays

    PMID:23620513

    Open questions at the time
    • Isoform differences in LRP1 competition not quantified here
    • Relationship to proteolytic clearance pathway not integrated
  7. 2013 Low

    Provided the structural rationale for isoform effects by showing the full-length two-domain ApoE3 structure propagates N-terminal mutations to the C-terminal domain.

    Evidence Review/analysis of a prior structure determination of full-length apoE3

    PMID:24115173

    Open questions at the time
    • Review/perspective without new experimental data; structural claim not directly verifiable from this source
    • No direct functional mapping of domain communication to receptor binding
  8. 2016 Medium

    Placed ApoE genetically downstream of PCSK9 by showing ApoE is required for PCSK9-driven hepatic lipogenesis, defining an ApoE-dependent arm of dyslipidemia.

    Evidence Transgenic hPCSK9 mice on WT, LDLR-/-, and apoE-/- backgrounds with plasma lipid and hepatic expression analysis

    PMID:26980204

    Open questions at the time
    • Mechanism by which ApoE enables PCSK9-driven lipogenesis not defined
    • Single lab
  9. 2019 High

    Revealed a non-lipid function of ApoE as a high-affinity inhibitor of the classical complement cascade through direct C1q binding, establishing ApoE as a complement checkpoint.

    Evidence SPR KD determination, C1q-ApoE complex immunostaining in human/mouse tissue, C5 siRNA knockdown, and ApoE-/- choroid plexus inflammation analysis

    PMID:30692699

    Open questions at the time
    • Isoform-specific differences in C1q inhibition not delineated
    • Structural basis of ApoE-C1q binding unresolved
  10. 2022 High

    Uncovered a cell-intrinsic pro-senescence role for APOE, showing its accumulation destabilizes heterochromatin via autophagy-lysosomal degradation of lamin and KAP1.

    Evidence CRISPR-Cas9 APOE knockout in human MPCs, aging/stress models, immunoblot/immunofluorescence for lamin and KAP1, and autophagy-lysosome inhibition

    PMID:37117743

    Open questions at the time
    • How secreted/intracellular APOE triggers lysosomal targeting of nuclear proteins is unclear
    • Isoform dependence of senescence phenotype not addressed
  11. 2023 Medium

    Identified mitochondrial/ETC dysfunction as an upstream driver of APOE induction, placing APOE within an inflammatory transcriptional response to bioenergetic stress.

    Evidence Gene editing of SLC25A transporters and ETC inhibition in iPSC-derived astrocytes and other cells with qRT-PCR/ELISA, plus 5xFAD mouse brain immunoblots

    PMID:37171075

    Open questions at the time
    • Direct transcriptional link between ETC state and APOE promoter not elucidated
    • Single lab
  12. 2024 High

    Connected isoform-graded LDLR binding to neuronal lipid pathology, showing impaired LDLR binding (ApoE2, Christchurch) is protective while ApoE4 promotes lysosomal lipofuscinosis and tau fibril retention.

    Evidence iPSC-derived human neurons with LDLR binding and cholesteryl ester uptake assays, lipofuscin and tau fibril readouts, and intrahippocampal PUFA-CE-lipApoE4 injection in mice

    PMID:39532095

    Open questions at the time
    • Mechanism linking lipofuscin to tau retention not fully resolved
    • Generalizability of injection sufficiency to physiological aging unclear
  13. 2024 Medium

    Demonstrated that specific APOE coding variants quantitatively shift LDLR binding affinity, providing functional grounding for variant contributions to dysbetalipoproteinemia.

    Evidence In vitro VLDL-to-LDLR binding affinity assays with patient-derived variants and NMR lipoprotein particle analysis

    PMID:37051929

    Open questions at the time
    • Single lab with limited mechanistic follow-up
    • In vivo consequences of intermediate-affinity variants not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single protein integrates lipid transport, receptor binding, complement inhibition, and chromatin-destabilizing senescence into the allele-specific risk for Alzheimer's and cardiovascular disease remains unresolved.
  • No unified structural-functional model linking isoform differences across all described activities
  • Relative contribution of each pathway to disease risk in vivo undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140104 molecular carrier activity 3 GO:0008289 lipid binding 2 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0005764 lysosome 1
Partners
ABCA1APOA1C1QLDLRLRP1PCSK9

Evidence

Reading pass · 13 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 ApoE facilitates the proteolytic clearance of soluble Aβ from the brain: endolytic degradation of Aβ within microglia by neprilysin is dramatically enhanced by ApoE, and extracellular Aβ degradation by insulin-degrading enzyme is also facilitated by ApoE. This capacity depends on ApoE isoform and lipidation status. Activation of liver X receptors (LXR) increases lipidated ApoE and stimulates Aβ degradation in vivo. In vitro degradation assays with microglia and purified enzymes; LXR agonist treatment of Tg2576 mice with measurement of brain Aβ load and contextual memory Neuron High 18549781
2013 ApoE does not directly bind soluble Aβ to an appreciable extent in solution or in human CSF. Instead, apoE regulates soluble Aβ metabolism by competing with Aβ for LRP1-dependent cellular uptake in astrocytes, thereby modulating Aβ clearance without requiring direct apoE–Aβ complex formation in extracellular fluids. Multiple biochemical and analytical techniques (SEC, native PAGE, SPR); brain Aβ microdialysis in mice receiving apoE infusions; LRP1 competition assays in astrocytes Proceedings of the National Academy of Sciences of the United States of America High 23620513
1999 ApoE3, but not ApoE4, protects against excitotoxin-induced and age-dependent neurodegeneration in mouse brain. Expression of human apoE3 in Apoe-/- mice preserved synaptophysin-positive presynaptic terminals, MAP2-positive dendrites, and neurofilament-positive axons after kainic acid challenge, whereas apoE4 did not. Neuron-specific enolase promoter-driven expression of human apoE3 or apoE4 in Apoe-/- mice; kainic acid challenge; immunohistochemical quantification of synaptic and dendritic markers The Journal of neuroscience : the official journal of the Society for Neuroscience High 10366621
2019 All human ApoE isoforms directly inhibit the classical complement cascade (CCC) by binding with high affinity (KD ~140–580 pM) to activated C1q, forming ApoE–C1q complexes. In ApoE-deficient mice, oxidized lipids activate the CCC, causing leukocyte infiltration; ApoE suppresses this by acting as a direct checkpoint inhibitor of complement activation. In vitro binding assays (SPR/biophysical measurement of KD); immunostaining of C1q-ApoE complexes in human and mouse tissue; siRNA knockdown of C5 in mice; analysis of ApoE-/- mouse choroid plexus inflammation Nature medicine High 30692699
1999 Truncated ApoE (22 kDa N-terminal fragment) and ApoE-derived peptides cause neurotoxicity and increases in intracellular calcium in embryonic rat hippocampal neurons. The calcium influx and cell death are reduced by receptor-associated protein (RAP), removal of extracellular calcium, or the NMDA receptor antagonist MK-801, indicating involvement of cell-surface receptors including NMDA receptors. Primary embryonic rat hippocampal neuron culture; intracellular calcium imaging; pharmacological inhibition with RAP and MK-801; protease inhibitor experiments The Journal of neuroscience : the official journal of the Society for Neuroscience Medium 10436064
2004 ApoE3 forms a direct complex with ABCA1 on the surface of intact fibroblasts. Lipid-free apoE3 competes with apoA-I for ABCA1 binding and promotes ABCA1-dependent cholesterol efflux. This interaction generates nascent apoE/cholesterol/phospholipid particles of 9–15 nm with prebeta electrophoretic mobility. A Tangier disease mutation in ABCA1 (C1477R) abolishes both apoE3 binding and apoE3-mediated cholesterol efflux, demonstrating that ABCA1 is essential for biogenesis of apoE-containing HDL-sized particles. 125I-apoA-I competition binding assays; cholesterol efflux assays with ABCA1 mutant cells; native PAGE sizing of nascent particles; stimulated intact human fibroblasts Journal of lipid research High 14754908
2022 APOE accumulation in aged human mesenchymal progenitor cells (MPCs) drives cellular senescence by destabilizing heterochromatin. Mechanistically, increased APOE causes autophagy-lysosomal pathway-dependent degradation of nuclear lamina proteins and the heterochromatin-associated protein KAP1 (KRAB-associated protein 1), thereby disrupting heterochromatin organization. CRISPR-Cas9 deletion of APOE confers resistance to senescence in human MPCs. CRISPR-Cas9 knockout of APOE in human MPCs; stress-induced and physiological aging models; immunoblot and immunofluorescence for lamin and KAP1; autophagy-lysosome pathway inhibition experiments Nature aging High 37117743
2024 Lipidated ApoE2 (lipApoE2) has impaired binding to the LDL receptor (LDLR) compared with lipApoE3/4, which avoids LDLR recycling defects and reduces uptake of cholesteryl esters (CEs) into neurons. In human neurons, ApoE carrying polyunsaturated fatty acid-CE (PUFA-CE) causes lysosomal lipofuscinosis in an allelic series (ApoE4 > ApoE3 > ApoE2); lipofuscin accumulation promotes lysosomal retention of tau fibrils. The protective Christchurch mutation also reduces LDLR binding and phenocopies ApoE2. Intrahippocampal injection of PUFA-CE-lipApoE4 alone is sufficient to induce lipofuscinosis in wild-type mice. iPSC-derived human neurons; LDLR binding assays; cholesteryl ester uptake measurements; lipofuscin quantification; tau fibril lysosomal assay; intrahippocampal injection in mice; 5xFAD mouse brain analysis Cell High 39532095
2023 Mitochondrial dysfunction (genetic disruption of SLC25A transporters or pharmacological/genetic inhibition of electron transport chain complexes I, III, or IV) causes upregulation of APOE transcript, protein, and secretion (up to 49-fold) in diverse cell types including iPSC-derived human astrocytes, as part of an inflammatory gene expression program. Age- and genotype-dependent decline in respiratory complex I preceded increased APOE in the 5xFAD mouse brain. Gene editing of SLC25A transporters; pharmacological ETC inhibition; iPSC-derived astrocytes; qRT-PCR and ELISA for APOE; 5xFAD mouse brain immunoblots eLife Medium 37171075
2013 The structure of full-length apoE3 (two-domain protein, 34 kDa) was determined and showed that mutations in the N-terminal domain can be propagated through the structure to the C-terminal domain. The single amino acid difference between apoE3 and apoE4 underlies structural differences relevant to their distinct disease-related functions. Review/analysis of 2011 structure determination; structural interpretation of isoform differences Protein science : a publication of the Protein Society Low 24115173
2024 ApoE variants affecting VLDL binding affinity to the LDL receptor were directly assayed in vitro. Variants p.(Arg163Cys) and p.(Arg165Trp) showed intermediate LDLR affinity between APOE2/2 and APOE3/3, while p.(Gly145Asp) and p.(Pro220Leu) showed higher affinity than APOE3/3, demonstrating that specific APOE coding variants alter receptor-binding function and contribute to dysbetalipoproteinemia. In vitro VLDL-to-LDLR binding affinity assay with patient-derived variants; NMR lipoprotein particle analysis Arteriosclerosis, thrombosis, and vascular biology Medium 37051929
2016 PCSK9 increases hepatic lipid and lipoprotein production via mechanisms dependent on both LDLR and apoE. In transgenic mice expressing human PCSK9 on an apoE-null background, the lipid-raising effect of PCSK9 is abolished, demonstrating that apoE is required for PCSK9-mediated hepatic lipogenesis and dyslipidemia. Transgenic hPCSK9 mice on WT, LDLR-/-, and apoE-/- backgrounds; plasma lipid measurement; hepatic gene expression analysis Cardiovascular research Medium 26980204
2000 Somatic gene transfer of human APOE cDNA via adenoviral vector into ApoE-deficient nude mice restored plasma apoE secretion, normalized hypercholesterolemia within 14 days, and induced dose-dependent regression of pre-existing fatty streak lesions in the aorta, demonstrating that apoE expression is sufficient to reverse atherosclerotic lesions. Adenoviral gene transfer into ApoE-/- nude mice; plasma cholesterol and triglyceride measurement; aortic lesion quantification Arteriosclerosis, thrombosis, and vascular biology Medium 10669641

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 ApoE promotes the proteolytic degradation of Abeta. Neuron 736 18549781
2013 ApoE influences amyloid-β (Aβ) clearance despite minimal apoE/Aβ association in physiological conditions. Proceedings of the National Academy of Sciences of the United States of America 457 23620513
1999 Expression of human apolipoprotein E3 or E4 in the brains of Apoe-/- mice: isoform-specific effects on neurodegeneration. The Journal of neuroscience : the official journal of the Society for Neuroscience 286 10366621
2019 ApoE attenuates unresolvable inflammation by complex formation with activated C1q. Nature medicine 238 30692699
1977 The initiation sites for RNA transcription in Ad2 DNA. Cell 200 922890
2016 The role of APOE in cerebrovascular dysfunction. Acta neuropathologica 195 26884068
2016 Do the Apoe-/- and Ldlr-/- Mice Yield the Same Insight on Atherogenesis? Arteriosclerosis, thrombosis, and vascular biology 160 27386935
2024 Multifaceted roles of APOE in Alzheimer disease. Nature reviews. Neurology 137 38906999
1999 Truncated apolipoprotein E (ApoE) causes increased intracellular calcium and may mediate ApoE neurotoxicity. The Journal of neuroscience : the official journal of the Society for Neuroscience 133 10436064
2017 ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease. Trends in endocrinology and metabolism: TEM 129 28057414
2009 Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-/- and apoE-/- mice. Journal of lipid research 125 19174369
2020 Formononetin attenuates atherosclerosis via regulating interaction between KLF4 and SRA in apoE-/- mice. Theranostics 116 31938053
2020 APOE in the normal brain. Neurobiology of disease 113 31911114
2001 Lipoprotein size and atherosclerosis susceptibility in Apoe(-/-) and Ldlr(-/-) mice. Arteriosclerosis, thrombosis, and vascular biology 112 11597927
2004 Molecular interactions between apoE and ABCA1: impact on apoE lipidation. Journal of lipid research 110 14754908
2016 Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms. Cardiovascular research 95 26980204
2008 APOE, APOE promoter, and Tau genotypes and risk for concussion in college athletes. Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine 93 18185033
2013 BAFF receptor mAb treatment ameliorates development and progression of atherosclerosis in hyperlipidemic ApoE(-/-) mice. PloS one 88 23560095
1996 Comparative analysis of adenovirus fiber-cell interaction: adenovirus type 2 (Ad2) and Ad9 utilize the same cellular fiber receptor but use different binding strategies for attachment. Journal of virology 87 8892881
2022 Destabilizing heterochromatin by APOE mediates senescence. Nature aging 85 37117743
2018 AIM2 accelerates the atherosclerotic plaque progressions in ApoE-/- mice. Biochemical and biophysical research communications 81 29510138
2010 Tanshinone IIA attenuates atherosclerosis in ApoE(-/-) mice through down-regulation of scavenger receptor expression. European journal of pharmacology 77 20854809
2018 ApoE and Neurodegenerative Diseases in Aging. Advances in experimental medicine and biology 71 30232753
2005 apoE isoforms and measures of anxiety in probable AD patients and Apoe-/- mice. Neurobiology of aging 70 15708438
2015 Endothelial NADPH oxidase 4 protects ApoE-/- mice from atherosclerotic lesions. Free radical biology & medicine 68 26169727
2024 Decreased lipidated ApoE-receptor interactions confer protection against pathogenicity of ApoE and its lipid cargoes in lysosomes. Cell 65 39532095
2015 IL-9 aggravates the development of atherosclerosis in ApoE-/- mice. Cardiovascular research 64 25784693
2012 Local heart irradiation of ApoE(-/-) mice induces microvascular and endocardial damage and accelerates coronary atherosclerosis. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 63 22959484
2012 The apolipoprotein E (APOE) gene appears functionally monomorphic in chimpanzees (Pan troglodytes). PloS one 62 23112842
2023 Butyrate suppresses atherosclerotic inflammation by regulating macrophages and polarization via GPR43/HDAC-miRNAs axis in ApoE-/- mice. PloS one 59 36888629
2010 Mast cell chymase inhibition reduces atherosclerotic plaque progression and improves plaque stability in ApoE-/- mice. Cardiovascular research 59 20693162
2002 APOE-epsilon4 and APOE -491A polymorphisms in individuals with subjective memory loss. Molecular psychiatry 59 12192621
2015 High-methionine diets accelerate atherosclerosis by HHcy-mediated FABP4 gene demethylation pathway via DNMT1 in ApoE(-/-) mice. FEBS letters 54 26606905
2014 Baicalin and geniposide attenuate atherosclerosis involving lipids regulation and immunoregulation in ApoE-/- mice. European journal of pharmacology 54 24991786
1975 Adenovirus transcription. II. RNA sequences complementary to simian virus 40 and adenovirus 2DNA in AD2+ND1- and AD2+ND3-infected cells. Journal of virology 54 169392
2017 Human Plasma Thioredoxin-80 Increases With Age and in ApoE-/- Mice Induces Inflammation, Angiogenesis, and Atherosclerosis. Circulation 53 28473446
1991 Purification and characterization of haloalcohol dehalogenase from Arthrobacter sp. strain AD2. Journal of bacteriology 53 1846134
2000 Complete atherosclerosis regression after human ApoE gene transfer in ApoE-deficient/nude mice. Arteriosclerosis, thrombosis, and vascular biology 52 10669641
2020 Acacetin exerts antioxidant potential against atherosclerosis through Nrf2 pathway in apoE-/- Mice. Journal of cellular and molecular medicine 51 33241629
2018 Geniposide regulates the miR-101/MKP-1/p38 pathway and alleviates atherosclerosis inflammatory injury in ApoE-/- mice. Immunobiology 51 30630636
2021 Identification of epigenome-wide DNA methylation differences between carriers of APOE ε4 and APOE ε2 alleles. Genome medicine 50 33397400
2024 Activation of Nrf2 inhibits atherosclerosis in ApoE-/- mice through suppressing endothelial cell inflammation and lipid peroxidation. Redox biology 45 38870781
2020 Inhibition of JAK2 Suppresses Myelopoiesis and Atherosclerosis in Apoe-/- Mice. Cardiovascular drugs and therapy 44 32086626
2019 Inflammation inhibition and gut microbiota regulation by TSG to combat atherosclerosis in ApoE-/- mice. Journal of ethnopharmacology 43 31606534
2018 Haplotype analysis of APOE intragenic SNPs. BMC neuroscience 42 29745836
2013 Mercury, APOE, and children's neurodevelopment. Neurotoxicology 41 23603214
2020 TSP-1 (Thrombospondin-1) Deficiency Protects ApoE-/- Mice Against Leptin-Induced Atherosclerosis. Arteriosclerosis, thrombosis, and vascular biology 40 33327743
2012 Apolipoprotein E gene (APOE) genotype in Wilson's disease: impact on clinical presentation. Parkinsonism & related disorders 40 22221592
2012 Genomics of Dementia: APOE- and CYP2D6-Related Pharmacogenetics. International journal of Alzheimer's disease 40 22482072
2024 Targeted delivery of MerTK protein via cell membrane engineered nanoparticle enhances efferocytosis and attenuates atherosclerosis in diabetic ApoE-/- Mice. Journal of nanobiotechnology 39 38614985
2021 FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE-/- mice atherosclerosis. Laboratory investigation; a journal of technical methods and pathology 38 34725437
2017 Asperlin Inhibits LPS-Evoked Foam Cell Formation and Prevents Atherosclerosis in ApoE-/- Mice. Marine drugs 38 29135917
2016 Sex and APOE: A memory advantage in male APOE ε4 carriers in midlife. Cortex; a journal devoted to the study of the nervous system and behavior 38 28086184
1979 Cell surface location of simian virus 40-specific proteins on HeLa cells infected with adenovirus type 2-simian virus 40 hybrid viruses Ad2+ND1 and Ad2+ND2. Journal of virology 38 90174
2011 Npp1 promotes atherosclerosis in ApoE knockout mice. Journal of cellular and molecular medicine 36 21477221
2020 Astragalus Flavone Ameliorates Atherosclerosis and Hepatic Steatosis Via Inhibiting Lipid-Disorder and Inflammation in apoE-/- Mice. Frontiers in pharmacology 34 33381046
2017 Celosins inhibit atherosclerosis in ApoE-/- mice and promote autophagy flow. Journal of ethnopharmacology 33 29292046
2013 Concerning the structure of apoE. Protein science : a publication of the Protein Society 33 24115173
2012 Ginkgolide B reduces atherogenesis and vascular inflammation in ApoE(-/-) mice. PloS one 33 22662117
2004 The role of viruses and of APOE in dementia. Annals of the New York Academy of Sciences 33 15246985
2007 Oxidatively damaged DNA in aging dyslipidemic ApoE-/- and wild-type mice. Mutagenesis 32 17234687
1998 The AD1 and AD2 transactivation domains of E2A are essential for the antiapoptotic activity of the chimeric oncoprotein E2A-HLF. Molecular and cellular biology 32 9742120
2020 Protocatechuic Acid Inhibits Vulnerable Atherosclerotic Lesion Progression in Older Apoe-/- Mice. The Journal of nutrition 31 32047914
2019 Metformin Therapy Aggravates Neurodegenerative Processes in ApoE-/- Mice. Journal of Alzheimer's disease : JAD 31 30909226
2023 APOE expression and secretion are modulated by mitochondrial dysfunction. eLife 30 37171075
2022 APOE genetics influence murine gut microbiome. Scientific reports 30 35115575
2019 Tanshinone IIA Promotes Macrophage Cholesterol Efflux and Attenuates Atherosclerosis of apoE-/- Mice by Omentin-1/ABCA1 Pathway. Current pharmaceutical biotechnology 30 30947667
2012 The comprehensive effects of hyperlipidemia and hyperhomocysteinemia on pathogenesis of atherosclerosis and DNA hypomethylation in ApoE-/- mice. Acta biochimica et biophysica Sinica 30 23017835
2024 Advancements in APOE and dementia research: Highlights from the 2023 AAIC Advancements: APOE conference. Alzheimer's & dementia : the journal of the Alzheimer's Association 28 39031528
2023 APOE and immunity: Research highlights. Alzheimer's & dementia : the journal of the Alzheimer's Association 27 36975090
2007 The missing ApoE allele. Annals of human genetics 26 17244188
2019 Adipokine Chemerin Stimulates Progression of Atherosclerosis in ApoE-/- Mice. BioMed research international 25 31781638
2017 Berberine ameliorates non-alcoholic steatohepatitis in ApoE-/- mice. Experimental and therapeutic medicine 25 29075339
2012 The methyl xanthine caffeine inhibits DNA damage signaling and reactive species and reduces atherosclerosis in ApoE(-/-) mice. Arteriosclerosis, thrombosis, and vascular biology 25 22859494
2011 The neurobiology of APOE in schizophrenia and mood disorders. Frontiers in bioscience (Landmark edition) 25 21196212
2023 Contribution of APOE Genetic Variants to Dyslipidemia. Arteriosclerosis, thrombosis, and vascular biology 23 37051929
2022 Genetic disruption of the Gipr in Apoe-/- mice promotes atherosclerosis. Molecular metabolism 23 36055579
2021 Myeloid cell-specific Irf5 deficiency stabilizes atherosclerotic plaques in Apoe-/- mice. Molecular metabolism 23 33991749
2021 Antiatherosclerotic effect of dehydrocorydaline on ApoE-/- mice: inhibition of macrophage inflammation. Acta pharmacologica Sinica 23 34552216
2020 Angiopoietin-like protein 8 accelerates atherosclerosis in ApoE-/- mice. Atherosclerosis 23 32739681
2018 Postnatal chlorpyrifos exposure and apolipoprotein E (APOE) genotype differentially affect cholinergic expression and developmental parameters in transgenic mice. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 23 29729306
2000 Apolipoprotein E (APOE) phenotype and APOE concentrations in multiple sclerosis and acute herpes zoster. Acta neurologica Scandinavica 23 10949525
1976 Simian virus 40-specific polypeptides in AD2+ ND1- and Ad2+ ND4-infected cells. Journal of virology 23 178903
2021 Lycopene Reduces Cholesterol Absorption and Prevents Atherosclerosis in ApoE-/- Mice by Downregulating HNF-1α and NPC1L1 Expression. Journal of agricultural and food chemistry 22 34428895
2016 Map3k8 Modulates Monocyte State and Atherogenesis in ApoE-/- Mice. Arteriosclerosis, thrombosis, and vascular biology 22 27856455
2015 The leukotriene B4 receptor (BLT) antagonist BIIL284 decreases atherosclerosis in ApoE-/- mice. Prostaglandins & other lipid mediators 22 26051858
2008 Regulated proteolysis of APP and ApoE receptors. Molecular neurobiology 22 18415033
2020 Downregulation of G3BP2 reduces atherosclerotic lesions in ApoE-/- mice. Atherosclerosis 21 32919187
2015 Chitosan Oligosaccharides Attenuate Atherosclerosis and Decrease Non-HDL in ApoE-/- Mice. Journal of atherosclerosis and thrombosis 21 25843117
2015 SAP deficiency mitigated atherosclerotic lesions in ApoE(-/-) mice. Atherosclerosis 21 26649902
2007 Analyses of variants located in estrogen metabolism genes (ESR1, ESR2, COMT and APOE) and schizophrenia. Schizophrenia research 21 18164902
2023 The Impact of Apolipoprotein E (APOE) Epigenetics on Aging and Sporadic Alzheimer's Disease. Biology 20 38132357
2020 Myriocin and d-PDMP ameliorate atherosclerosis in ApoE-/- mice via reducing lipid uptake and vascular inflammation. Clinical science (London, England : 1979) 20 32091078
2008 Amyloid precursor protein mediates monocyte adhesion in AD tissue and apoE(-)/(-) mice. Neurobiology of aging 20 19058878
2021 Pharmacological inhibition of IRAK1 and IRAK4 prevents endothelial inflammation and atherosclerosis in ApoE-/- mice. Pharmacological research 19 34954030
2019 Immunohistochemical biomarkers and distribution of telocytes in ApoE-/- mice. Cell biology international 19 30912221
2016 The anti-inflammatory vasostatin-2 attenuates atherosclerosis in ApoE-/- mice and inhibits monocyte/macrophage recruitment. Thrombosis and haemostasis 19 27831589
2020 Plasma APE1/Ref-1 Correlates with Atherosclerotic Inflammation in ApoE-/- Mice. Biomedicines 18 32967121
2016 TRAF3IP2 mediates atherosclerotic plaque development and vulnerability in ApoE(-/-) mice. Atherosclerosis 18 27237075
2015 The association of apolipoprotein E (APOE) gene polymorphisms with atherosclerosis susceptibility: a meta-analysis. Minerva cardioangiologica 17 26005211

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