Research graph
References from Emerging therapeutic strategies to target APOE4 in Alzheimer's disease. Local targets link to admitted publications; unresolved targets remain external evidence.
Apolipoprotein E: high‐avidity binding to beta‐amyloid and increased frequency of type 4 allele in late‐onset familial Alzheimer disease
10.1073/pnas.90.5.1977 · 1993 · External reference
Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families
10.1126/science.8346443 · 1993 · External reference
Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta‐analysis. APOE and Alzheimer disease meta analysis consortium
10.1001/jama.1997.03550160069041 · 1997 · External reference
Report of the APOE4 National Institute on Aging/Alzheimer disease sequencing project consortium working group: reducing APOE4 in carriers is a therapeutic goal for Alzheimer's disease
10.1002/ana.26864 · 2024 · External reference
APOE4 homozygozity represents a distinct genetic form of Alzheimer's disease
10.1038/s41591-024-02931-w · 2024 · External reference
Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies
10.1038/s41582-019-0228-7 · 2019 · External reference
APOE and Alzheimer disease: a major gene with semi‐dominant inheritance
10.1038/mp.2011.52 · 2011 · External reference
Cell type‐specific roles of APOE4 in Alzheimer disease
10.1038/s41583-023-00776-9 · 2024 · External reference
Multifaceted roles of APOE in Alzheimer disease
10.1038/s41582-024-00988-2 · 2024 · External reference
The cell biology of APOE in the brain
10.1016/j.tcb.2023.09.004 · 2024 · External reference
Introduction of human apolipoprotein E4 “domain interaction” into mouse apolipoprotein E
10.1073/pnas.201279298 · 2001 · External reference
Mechanism underlying apolipoprotein E (ApoE) isoform‐dependent lipid efflux from neural cells in culture
10.1002/jnr.22073 · 2009 · External reference
Structure‐dependent impairment of intracellular apolipoprotein E4 trafficking and its detrimental effects are rescued by small‐molecule structure correctors
10.1074/jbc.m110.217380 · 2011 · External reference
APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
10.1038/s41586-022-05439-w · 2022 · External reference
Triglyceride metabolism controls inflammation and microglial phenotypes associated with APOE4
10.1016/j.celrep.2025.115961 · 2025 · External reference
APOE4/4 is linked to damaging lipid droplets in Alzheimer's disease microglia
10.1038/s41586-024-07185-7 · 2024 · External reference
Lipid‐ and receptor‐binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity
10.1073/pnas.0508254102 · 2005 · External reference
Proteolytic cleavage of apolipoprotein E4 as the keystone for the heightened risk associated with Alzheimer's disease
10.3390/ijms140714908 · 2013 · External reference
Carboxyl‐terminal‐truncated apolipoprotein E4 causes Alzheimer's disease‐like neurodegeneration and behavioral deficits in transgenic mice
10.1073/pnas.1434398100 · 2003 · External reference
10.64898/2026.07.15.738801
10.64898/2026.07.15.738801 · External reference
ApoE4 markedly exacerbates tau‐mediated neurodegeneration in a mouse model of tauopathy
10.1038/nature24016 · 2017 · External reference
Human apoE isoforms differentially regulate brain amyloid‐β peptide clearance
10.1126/scitranslmed.3002156 · 2011 · External reference
apoE isoform‐specific disruption of amyloid beta peptide clearance from mouse brain
10.1172/jci36663 · 2008 · External reference
Apolipoprotein E: a pathological chaperone protein in patients with cerebral and systemic amyloid
10.1016/0304-3940(92)90444-c · 1992 · External reference
Differential and substrate‐specific inhibition of γ‐secretase by the C‐terminal region of ApoE2, ApoE3, and ApoE4
10.1016/j.neuron.2023.03.024 · 2023 · External reference
Direct and potent regulation of gamma‐secretase by its lipid microenvironment
10.1074/jbc.m801925200 · 2008 · External reference
Cholesterol‐dependent gamma‐secretase activity in buoyant cholesterol‐rich membrane microdomains
10.1006/nbdi.2001.0470 · 2002 · External reference
Neuronal ApoE4 stimulates C/EBPβ activation, promoting Alzheimer's disease pathology in a mouse model
10.1016/j.pneurobio.2021.102212 · 2022 · External reference
ApoE attenuates unresolvable inflammation by complex formation with activated C1q
10.1038/s41591-018-0336-8 · 2019 · External reference
TREM2 binds to apolipoproteins, including APOE and CLU/APOJ, and thereby facilitates uptake of amyloid‐Beta by microglia
10.1016/j.neuron.2016.06.015 · 2016 · External reference
LilrB3 is a putative cell surface receptor of APOE4
10.1038/s41422-022-00759-y · 2023 · External reference
From genetics to neuroinflammation: the impact of ApoE4 on microglial function in Alzheimer's disease
10.3390/cells14040243 · 2025 · External reference
APOE4 reprograms microglial lipid metabolism in Alzheimer's disease: mechanisms and therapeutic implications
10.5582/bst.2025.01148 · 2026 · External reference
A unique microglia type associated with restricting development of Alzheimer's disease
10.1016/j.cell.2017.05.018 · 2017 · External reference
APOE4 leads to blood‐brain barrier dysfunction predicting cognitive decline
10.1038/s41586-020-2247-3 · 2020 · External reference
Accelerated pericyte degeneration and blood‐brain barrier breakdown in apolipoprotein E4 carriers with Alzheimer's disease
10.1038/jcbfm.2015.44 · 2016 · External reference
Apolipoprotein E controls cerebrovascular integrity via cyclophilin a
10.1038/nature11087 · 2012 · External reference
Apolipoprotein E4 produced in GABAergic interneurons causes learning and memory deficits in mice
10.1523/jneurosci.2281-14.2014 · 2014 · External reference
Apolipoprotein E4, inhibitory network dysfunction, and Alzheimer's disease
10.1186/s13024-019-0324-6 · 2019 · External reference
ApoE4 reduces glutamate receptor function and synaptic plasticity by selectively impairing ApoE receptor recycling
10.1073/pnas.0914984107 · 2010 · External reference
Therapeutic challenges derived from the interaction among apolipoprotein E, cholesterol, and amyloid in Alzheimer's disease
10.3390/ijms252212029 · 2024 · External reference
Gain of toxic apolipoprotein E4 effects in human iPSC‐derived neurons is ameliorated by a small‐molecule structure corrector
10.1038/s41591-018-0004-z · 2018 · External reference
APOE and Alzheimer's disease: advances in genetics, pathophysiology, and therapeutic approaches
10.1016/s1474-4422(20)30412-9 · 2021 · External reference
ApoE‐directed therapeutics rapidly clear β‐amyloid and reverse deficits in AD mouse models
10.1126/science.1217697 · 2012 · External reference
Amelioration of tau and ApoE4‐linked glial lipid accumulation and neurodegeneration with an LXR agonist
10.1016/j.neuron.2023.10.023 · 2024 · External reference
Apolipoprotein E and Alzheimer disease: risk, mechanisms and therapy
10.1038/nrneurol.2012.263 · 2013 · External reference
Small molecule structure correctors abolish detrimental effects of apolipoprotein E4 in cultured neurons
10.1074/jbc.m111.276162 · 2012 · External reference
Apolipoprotein (apo) E4 enhances amyloid beta peptide production in cultured neuronal cells: apoE structure as a potential therapeutic target
10.1073/pnas.0508693102 · 2005 · External reference
Discovery of Isobavachin, a natural flavonoid, as an apolipoprotein E4 (ApoE4) structure corrector for Alzheimer's disease
10.3390/molecules30040940 · 2025 · External reference
In silico identification of novel apolipoprotein E4 inhibitor for Alzheimer's disease therapy
10.2174/1573409914666181008164209 · 2019 · External reference
Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice
10.1016/j.neuropharm.2016.04.032 · 2016 · External reference
Effect of apoE genotype and dietary quercetin on blood lipids and TNF‐alpha levels in apoE3 and apoE4 targeted gene replacement mice
10.1017/s0007114508102434 · 2009 · External reference
The emerging role of CETP inhibition in the prevention of Alzheimer's disease
10.1016/j.ajpc.2026.101442 · 2026 · External reference
Effect of obicetrapib, a potent cholesteryl ester transfer protein inhibitor, on p‐tau217 levels in patients with cardiovascular disease
10.1016/j.tjpad.2025.100394 · 2026 · External reference
ApoE: in vitro studies of a Small molecule effector
10.1021/acs.biochem.6b00324 · 2016 · External reference
Endophenotype‐based in silico network medicine discovery combined with insurance record data mining identifies sildenafil as a candidate drug for Alzheimer's disease
10.1038/s43587-021-00138-z · 2021 · External reference
Lithium deficiency and the onset of Alzheimer's disease
10.1038/s41586-025-09335-x · 2025 · External reference
Protection against Alzheimer's disease with APOE Christchurch variant ‐ how?
10.1056/nejme2403712 · 2024 · External reference
APOE2: protective mechanism and therapeutic implications for Alzheimer's disease
10.1186/s13024-020-00413-4 · 2020 · External reference
Protective ApoE variants support neuronal function by effluxing oxidized phospholipids
10.1016/j.neuron.2025.10.040 · 2026 · External reference
Gene transfer of human Apoe isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain
10.1126/scitranslmed.3007000 · 2013 · External reference
AAVrh.10‐mediated APOE2 central nervous system gene therapy for APOE4‐associated Alzheimer's disease
10.1089/humc.2017.231 · 2018 · External reference
Apolipoprotein E2‐Christchurch (136 Arg—Ser). New variant of human apolipoprotein E in a patient with type III hyperlipoproteinemia
10.1172/jci113096 · 1987 · External reference
Resistance to autosomal dominant Alzheimer's disease in an APOE3 Christchurch homozygote: a case report
10.1038/s41591-019-0611-3 · 2019 · External reference
The APOE‐R136S mutation protects against APOE4‐driven Tau pathology, neurodegeneration and neuroinflammation
10.1038/s41593-023-01480-8 · 2023 · External reference
The R136S mutation in the APOE3 gene confers resilience against tau pathology via inhibition of the cGAS‐STING‐IFN pathway
10.1016/j.immuni.2025.05.023 · 2025 · External reference
APOE Christchurch‐mimetic therapeutic antibody reduces APOE‐mediated toxicity and tau phosphorylation
10.1002/alz.13436 · 2024 · External reference
APOE3ch alters microglial response and suppresses aβ‐induced tau seeding and spread
10.1016/j.cell.2023.11.029 · 2024 · External reference
Microglial APOE3 Christchurch protects neurons from tau pathology in a human iPSC‐based model of Alzheimer's disease
10.1016/j.celrep.2024.114982 · 2024 · External reference
Hepatic expression of APOE3 Christchurch mitigates APOE4‐related Alzheimer's disease pathologies in mice
2026 · External reference
APOE loss‐of‐function variants: compatible with longevity and associated with resistance to Alzheimer's disease pathology
10.1016/j.neuron.2024.01.008 · 2024 · External reference
Apolipoprotein (APOE) gene is associated with progression of age‐related macular degeneration (AMD)
10.1002/humu.20288 · 2006 · External reference
Whole‐genome sequencing analysis reveals new susceptibility loci and structural variants associated with progressive supranuclear palsy
10.1186/s13024-024-00747-3 · 2024 · External reference
A Spanish‐Portuguese GWAS of progressive supranuclear palsy reveals a novel risk locus in NFASC
10.1038/s41431-025-01872-3 · 2025 · External reference
Suppression of aging in mice by the hormone klotho
10.1126/science.1112766 · 2005 · External reference
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
10.1038/36285 · 1997 · External reference
Association of Klotho‐VS heterozygosity with risk of Alzheimer disease in individuals who carry APOE4
10.1001/jamaneurol.2020.0414 · 2020 · External reference
KLOTHO heterozygosity attenuates APOE4‐related amyloid burden in preclinical AD
10.1212/wnl.0000000000007323 · 2019 · External reference
Impact of APOE, klotho, and sex on cognitive decline with aging
10.1073/pnas.2416042122 · 2025 · External reference
Relationship of klotho with cognition and dementia: results from the NHANES 2011‐2014 and mendelian randomization study
10.1038/s41398-023-02632-x · 2023 · External reference
The relationship between serum klotho and cognitive performance in a nationally representative sample of US adults
10.3389/fnagi.2023.1053390 · 2023 · External reference
Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging
10.1007/s11682-016-9598-2 · 2017 · External reference
Caspase signalling controls microglia activation and neurotoxicity
10.1038/nature09788 · 2011 · External reference
A loss of function variant in CASP7 protects against Alzheimer's disease in homozygous APOE ε4 allele carriers
10.1186/s12864-016-2725-z · 2016 · External reference
Genome‐wide haplotype association study identify TNFRSF1A, CASP7, LRP1B, CDH1 and TG genes associated with Alzheimer's disease in Caribbean Hispanic individuals
10.18632/oncotarget.6391 · 2015 · External reference
Fibronectin at a glance
10.1242/jcs.00059 · 2002 · External reference
Rare genetic variation in fibronectin 1 (FN1) protects against APOEε4 in Alzheimer's disease
10.1007/s00401-024-02721-1 · 2024 · External reference
rs140926439 variant in the fibronectin FN1 gene lowers risk of Alzheimer disease in APOEε4 carriers in the UK biobank cohort
2025 · External reference
HIFalpha targeted for VHL‐mediated destruction by proline hydroxylation: implications for O2 sensing
10.1126/science.1059817 · 2001 · External reference
Von Hippel‐Lindau disease: insights into oxygen sensing, protein degradation, and cancer
10.1172/jci162480 · 2022 · External reference
Proteasomal regulation of the hypoxic response modulates aging in C. Elegans
10.1126/science.1173507 · 2009 · External reference
VHL‐1 inactivation and mitochondrial antioxidants rescue C. Elegans dopaminergic neurodegeneration
10.1007/s13238-019-0621-4 · 2019 · External reference
Suppressing APOE4‐induced neural pathologies by targeting the VHL‐HIF axis
10.1073/pnas.2417515122 · 2025 · External reference
Conserved lipid metabolic reprogramming confers hypoxic and aging resilience
10.1038/s44319-025-00664-6 · 2026 · External reference
Peripheral cancer attenuates amyloid pathology in Alzheimer's disease via cystatin‐c activation of TREM2
10.1016/j.cell.2025.12.020 · 2026 · External reference
Christianson syndrome protein NHE6 modulates TrkB endosomal signaling required for neuronal circuit development
10.1016/j.neuron.2013.07.043 · 2013 · External reference
Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH
10.1073/pnas.1801612115 · 2018 · External reference
Reversal of ApoE4‐induced recycling block as a novel prevention approach for Alzheimer's disease
10.7554/elife.40048 · 2018 · External reference
NHE6 depletion corrects ApoE4‐mediated synaptic impairments and reduces amyloid plaque load
10.7554/elife.72034 · 2021 · External reference
Genetic variants and haplotypes of TOMM40, APOE, and APOC1 are related to the age of onset of late‐onset Alzheimer disease in a Colombian population
10.1097/wad.0000000000000477 · 2022 · External reference
Resilience to autosomal dominant Alzheimer's disease in a reelin‐COLBOS heterozygous man
10.1038/s41591-023-02318-3 · 2023 · External reference
Alzheimer's protection by PLCγ2 compacts plaques, redistributes microglia, and protects synapses in AppNL ‐G‐F mice
10.1002/glia.70192 · 2026 · External reference
Silencing Apoe with divalent‐siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease
10.1002/alz.13703 · 2024 · External reference
Apolipoprotein E4 reduction with antisense oligonucleotides decreases neurodegeneration in a tauopathy model
10.1002/ana.26043 · 2021 · External reference
CRISPR‐based correction of apolipoprotein E4 in Alzheimer's disease: therapeutic strategies and macromolecular delivery innovations
10.1016/j.ijbiomac.2026.151352 · 2026 · External reference
APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease‐related metabolic signatures, neuropathology and cognition
10.1038/s41593-025-02094-y · 2025 · External reference
APOE4 causes widespread molecular and cellular alterations associated with Alzheimer's disease phenotypes in human iPSC‐derived brain cell types
10.1016/j.neuron.2018.05.008 · 2018 · External reference
Selection of rAAV vectors that cross the human blood‐brain barrier and target the central nervous system using a transwell model
10.1016/j.omtm.2022.09.002 · 2022 · External reference
Adeno‐associated virus as a delivery vector for gene therapy of human diseases
10.1038/s41392-024-01780-w · 2024 · External reference
Lipid nanoparticles and transcranial focused ultrasound enhance the delivery of SOD1 antisense oligonucleotides to the murine brain for ALS therapy
10.1016/j.jconrel.2024.11.074 · 2025 · External reference
Strategies for delivering therapeutics across the blood‐brain barrier
10.1038/s41573-021-00139-y · 2021 · External reference
Brain delivery of therapeutic proteins using an fc fragment blood‐brain barrier transport vehicle in mice and monkeys
10.1126/scitranslmed.aay1359 · 2020 · External reference
Engineered exosomes as precision tools for brain‐targeted drug delivery and treatment of central nervous system diseases
10.1016/j.celbio.2025.100344 · 2026 · External reference
10.1101/2024.04.23.590784
10.1101/2024.04.23.590784 · External reference
Apolipoprotein E: from cardiovascular disease to neurodegenerative disorders
10.1007/s00109-016-1427-y · 2016 · External reference
Generation of novel anti‐apoE monoclonal antibodies that selectively recognize apoE isoforms
10.1002/1873-3468.14858 · 2024 · External reference
Amyloid‐related imaging abnormalities and β‐amyloid‐targeting antibodies: a systematic review
10.1001/jamaneurol.2021.5205 · 2022 · External reference
An anti‐apoE4 specific monoclonal antibody counteracts the pathological effects of apoE4 in vivo
10.2174/1567205013666160404120817 · 2016 · External reference
Anti‐apoE immunotherapy inhibits amyloid accumulation in a transgenic mouse model of aβ amyloidosis
10.1084/jem.20121274 · 2012 · External reference
Targeting of nonlipidated, aggregated apoE with antibodies inhibits amyloid accumulation
10.1172/jci96429 · 2018 · External reference
10.64898/2026.05.20.726622
10.64898/2026.05.20.726622 · External reference
Neuronal APOE4 removal protects against tau‐mediated gliosis, neurodegeneration and myelin deficits
10.1038/s43587-023-00368-3 · 2023 · External reference
Blocking the apolipoprotein E/amyloid‐beta interaction as a potential therapeutic approach for Alzheimer's disease
10.1073/pnas.0604011103 · 2006 · External reference
Recombinant antibody fragments for neurodegenerative diseases
10.2174/1570159x01666160930121647 · 2017 · External reference
From whole monoclonal antibodies to single domain antibodies: think small
10.1007/978-1-61779-968-6_1 · 2012 · External reference
A nanobody‐based toolbox to probe ApoE4 in the secretory pathway and cytosol
10.3390/cells15050479 · 2026 · External reference
Bispecific brain‐penetrant antibodies for treatment of Alzheimer's disease
10.1016/j.tjpad.2025.100214 · 2025 · External reference
Recent advances in antibody therapy for Alzheimer's disease: focus on bispecific antibodies
10.3390/ijms26136271 · 2025 · External reference
Intradiabodies, bispecific, tetravalent antibodies for the simultaneous functional knockout of two cell surface receptors
10.1074/jbc.m307002200 · 2003 · External reference
APOE genotype and postnatal chlorpyrifos exposure modulate gut microbiota and cerebral short‐chain fatty acids in preweaning mice
10.1016/j.fct.2019.110872 · 2020 · External reference
Compositional and functional gut microbiota alterations in mild cognitive impairment: links to Alzheimer's disease pathology
10.1186/s13195-025-01769-9 · 2025 · External reference