ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Different mechanisms of apolipoprotein E isoform-dependent modulation of prostaglandin E2 production and triggering receptor expressed on myeloid cells 2 (TREM2) expression after innate immune activation of microglia.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- The multifaceted roles of apolipoprotein E4 in Alzheimer's disease pathology and potential therapeutic strategies.Cell death discovery · 2025Review
- Effects of the subtypes of apolipoprotein E on immune inhibition and prognosis in patients with Hepatocellular Carcinoma.Journal of cancer research and clinical oncology · 2024Article
- Multiple Roles of Apolipoprotein E4 in Oxidative Lipid Metabolism and Ferroptosis During the Pathogenesis of Alzheimer's Disease.Journal of molecular neuroscience : MN · 2024Review
- Roles of ApoE4 on the Pathogenesis in Alzheimer's Disease and the Potential Therapeutic Approaches.Cellular and molecular neurobiology · 2023Review
- Sex and APOE Genotype Alter the Basal and Induced Inflammatory States of Primary Microglia from APOE Targeted Replacement Mice.International journal of molecular sciences · 2022Article
- Article
- Lipid and Lipoprotein Metabolism in Microglia.Frontiers in physiology · 2020Review
- APOE genotype and sex affect microglial interactions with plaques in Alzheimer's disease mice.Acta neuropathologica communications · 2019Article
- APOE and Alzheimer's Disease: Evidence Mounts that Targeting APOE4 may Combat Alzheimer's Pathogenesis.Molecular neurobiology · 2019Review
- ApoE4: an emerging therapeutic target for Alzheimer's disease.BMC medicine · 2019Review
- Review
- Could Alzheimer's Disease Originate in the Periphery and If So How So?Molecular neurobiology · 2019Review
- New insights into the role of TREM2 in Alzheimer's disease.Molecular neurodegeneration · 2018Review
- ABCA1 haplodeficiency affects the brain transcriptome following traumatic brain injury in mice expressing human APOE isoforms.Acta neuropathologica communications · 2018Article
- Microglia-Mediated Neuroprotection, TREM2, and Alzheimer's Disease: Evidence From Optical Imaging.Biological psychiatry · 2018Review
- Loss of glutamate signaling from the thalamus to dorsal striatum impairs motor function and slows the execution of learned behaviors.NPJ Parkinson's disease · 2018Article
- The effects of apolipoprotein E genotype, α-synuclein deficiency, and sex on brain synaptic and Alzheimer's disease-related pathology.Alzheimer's & dementia (Amsterdam, Netherlands) · 2018Article
- Inflammation: Bridging Age, Menopause and APOEε4 Genotype to Alzheimer's Disease.Frontiers in aging neuroscience · 2018Review
- Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2017Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Several lines of evidence support immune response in brain as a mechanism of injury in Alzheimer disease (AD). Moreover, immune activation is heightened in apolipoprotein E (APOE) ε4 carriers; inhibitors of prostaglandin (PG) synthesis show a partially protective effect on AD risk from APOE ε4; and genetic variants in triggering receptor expressed on myeloid cells 2 (TREM2) are a rare but potent risk for AD. We tested the hypothesis that APOE ε4 inheritance modulates both the PGE2 pathway and TREM2 expression using primary murine microglia from targeted replacement (TR) APOE3/3 and APOE4/4 mice. Microglial cyclooxygenase-2, microsomal PGE synthase, and PGE2 expression were increased 2- to 25-fold in both genotypes by TLR activators; however, this induction was significantly (P < 0.01) greater in TR APOE4/4 microglia with TLR3 and TLR4 activators. Microglial TREM2 expression was reduced approximately 85% by all TLR activators; this reduction was approximately one-third greater in microglia from TR APOE4/4 mice. Importantly, both receptor-associated protein and a nuclear factor κ-light-chain-enhancer inhibitor blocked TR APOE4/4-dependent effects on the PGE2 pathway but not on TREM2 expression. These data demonstrate complementary, but mechanistically distinct, regulation of pro- and anti-inflammatory mediators in TR APOE4/4 murine microglia that yields a more proinflammatory state than with TR APOE3/3.
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