ArticleFrontiers in cellular neuroscience2019
Phagocytosis of Apoptotic Cells Is Specifically Upregulated in ApoE4 Expressing Microglia
Article in Frontiers in cellular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Disentangling the inverse relationship between cancer and Alzheimer's or Parkinson's disease: A systematic review on Mendelian randomization studies.Neurobiology of disease · 2025Pooled it
- Alzheimer's Disease Risk AllelebioRxiv : the preprint server for biology · 2026Article
- Adult neural stem cells mediate hippocampal synapse elimination for circuit homeostasis through MERTK.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- ApoE expression across the CNS: Who, What, Where, When, and How (much)?Molecular neurodegeneration advances · 2026Review
- Lysosomal proteomics reveals mechanisms of neuronal APOE4-associated lysosomal dysfunction.Autophagy · 2025Article
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- APOE4 impairs macrophage lipophagy and promotes demyelination of spiral ganglion neurons in mouse cochleae.Cell death discovery · 2025Article
- Multi-target approach to Alzheimer's disease prevention and treatment: antioxidant, anti-inflammatory, and amyloid- modulating mechanisms.Neurogenetics · 2025Review
- Lysosomal proteomics reveals mechanisms of neuronal apoE4-associated lysosomal dysfunction.bioRxiv : the preprint server for biology · 2025Article
- From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer's Disease.Cells · 2025Review
- Unraveling APOE4's Role in Alzheimer's Disease: Pathologies and Therapeutic Strategies.Current protein & peptide science · 2025Review
- Cell type-specific functions of Alzheimer's disease endocytic risk genes.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Review
- Cell type-specific roles of APOE4 in Alzheimer disease.Nature reviews. Neuroscience · 2024Review
- Editorial: Trends in neuroimmunology: cross-talk between brain-resident and peripheral immune cells in both health and disease.Frontiers in immunology · 2024Article
- APOE4-promoted gliosis and degeneration in tauopathy are ameliorated by pharmacological inhibition of HMGB1 release.Cell reports · 2023Article
- An aging, pathology burden, and glial senescence build-up hypothesis for late onset Alzheimer's disease.Nature communications · 2023Review
- A "multi-omics" analysis of blood-brain barrier and synaptic dysfunction in APOE4 mice.The Journal of experimental medicine · 2022Article
- A multi-hit hypothesis for an APOE4-dependent pathophysiological state.The European journal of neuroscience · 2022Review
- Assaying Microglia Functions In Vitro.Cells · 2022Review
- APOE4 confers transcriptomic and functional alterations to primary mouse microglia.Neurobiology of disease · 2022Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is characterized by intracellular tau aggregates and extracellular deposition of amyloid-β (Aβ). The major genetic risk factor to develop AD is the Apolipoprotein E isoform 4 (ApoE4). ApoE4 may directly affect Aβ pathology, yet the exact role of ApoE4 in the progression of AD remains unclear. Although astrocytes are the main source of ApoE in brain tissue, other cell types might contribute to ApoE isotype-dependent effects. While ApoE expression does not play a relevant role in homeostatic microglia, we and others could recently show that ApoE expression is significant upregulated in disease-associated microglia including AD-mouse models and human AD. ApoE has been supposed to have an anti-inflammatory effect, with ApoE4 being less effective than ApoE3. However, ApoE-isotype specific effects on microglia function in disease have not been thoroughly investigated to date. In contrast to this, the role of ApoE2, the third most common major ApoE isoform, in neurodegeneration has not been characterized in detail, but it has been shown to delay the onset of disease in familial AD. To elucidate the differential roles of the three-major human ApoE isoforms on microglia function we each expressed the human ApoE isoforms in murine N9 microglia cells. We could show that ApoE4 specifically influences actin cytoskeleton rearrangement and morphology. In migration assays, ApoE4 significantly promotes cell motility. To quantify phagocytosis by microglia we established an uptake assay based on imaging flow cytometry. Although expression of ApoE4 led to significantly reduced uptake of Aβ in contrast to the other isoforms, we could show that ApoE4 specifically increased phagocytosis of apoptotic neuronal cells. Our findings show that ApoE4 intrinsically affects microglia physiology by upregulating motility and phagocytic behavior
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