ArticleThe Journal of allergy and clinical immunology2014
APOε4 is associated with enhanced in vivo innate immune responses in human subjects.
Article in The Journal of allergy and clinical immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers.
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Who cites it
119 citing papers in PubMed, 187 citations in OpenAlex.
- Article
- Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement.Neurobiology of aging · 2026Article
- Cross-tissue immune profiling of APOE ε4 reveals early dysregulation in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Divergent biological consequences of APOE isoforms across industrialized and non-industrial environments.PLoS genetics · 2026Article
- Promotion of hepatitis B virus infection by extracellular apolipoprotein E.Journal of virology · 2026Article
- Intersectional effects of race/ethnicity, sex, and APOE4 on plasma inflammatory profiles in Hispanic and non-Hispanic white adults.Brain, behavior, & immunity - health · 2026Article
- Divergent Biological Consequences of APOE Isoforms Across Industrialized and Non-Industrial Environments.bioRxiv : the preprint server for biology · 2026Article
- Microbiota and Alzheimer's disease: mechanistic insights from a multi-organ perspective.Translational neurodegeneration · 2026Review
- Imaging research, diagnosis, and treatment advances of post-stroke cognitive impairment.Frontiers in neuroimaging · 2026Review
- Deciphering the role of APOE in cerebral amyloid angiopathy: from genetic insights to therapeutic horizons.Annals of medicine · 2025Review
- High-density lipoprotein: a biomarker and therapeutic target in sepsis.Critical care (London, England) · 2025Review
- The effect of APOE4 on Alzheimer's plasma biomarkers among Mexican Americans in the HABS-HD cohort.Alzheimer's research & therapy · 2025Article
- APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.Neurobiology of disease · 2025Article
- APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.Nature medicine · 2025Article
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype.Aging cell · 2025Article
- Microbial Trojan Horses: Virulence Factors as Key Players in Neurodegenerative Diseases.Molecules (Basel, Switzerland) · 2025Review
- Aging shapes baseline immunity in sterile-housed female hAPOE mouse genotypes.Journal of cellular and molecular immunology · 2025Article
- Article
- Midlife and late-life environmental exposures on dementia risk in the Wisconsin Longitudinal Study: The modifying effects of ApoE.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe genetic determinants of the human innate immune response are poorly understood. Apolipoprotein (Apo) E, a lipid-trafficking protein that affects inflammation, has well-described wild-type (ε3) and disease-associated (ε2 and ε4) alleles, but its connection to human innate immunity is undefined.
objectiveWe sought to define the relationship of APOε4 to the human innate immune response.
methodsWe evaluated APOε4 in several functional models of the human innate immune response, including intravenous LPS challenge in human subjects, and assessed APOε4 association to organ injury in patients with severe sepsis, a disease driven by dysregulated innate immunity.
resultsWhole blood from healthy APOε3/APOε4 volunteers induced higher cytokine levels on ex vivo stimulation with Toll-like receptor (TLR) 2, TLR4, or TLR5 ligands than blood from APOε3/APOε3 patients, whereas TLR7/8 responses were similar. This was associated with increased lipid rafts in APOε3/APOε4 monocytes. By contrast, APOε3/APOε3 and APOε3/APOε4 serum neutralized LPS equivalently and supported similar LPS responses in Apoe-deficient macrophages, arguing against a differential role for secretory APOE4 protein. After intravenous LPS, APOε3/APOε4 patients had higher hyperthermia and plasma TNF-α levels and earlier plasma IL-6 than APOε3/APOε3 patients. APOE4-targeted replacement mice displayed enhanced hypothermia, plasma cytokines, and hepatic injury and altered splenic lymphocyte apoptosis after systemic LPS compared with APOE3 counterparts. In a cohort of 828 patients with severe sepsis, APOε4 was associated with increased coagulation system failure among European American patients.
conclusionsAPOε4 is a determinant of the human innate immune response to multiple TLR ligands and associates with altered patterns of organ injury in human sepsis.
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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.