ArticleNature immunology2023
Cell-autonomous effects of APOE4 in restricting microglial response in brain homeostasis and Alzheimer's disease.
Article in Nature immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
102 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Pooled it
- Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement.Neurobiology of aging · 2026Article
- Review
- APOE3 and APOE4 human astrocytes differentially modulate Alzheimer's disease pathology and microglial responses in chimeric mice.Cell reports · 2026Article
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- Review
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Age at menopause,Research square · 2026Article
- Article
- Reshaping the immune landscape: next-generation microglia-targeted therapies for Alzheimer's disease.Biological research · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Aortic Single-Cell Transcriptome Analysis Reveals ApoE-Isoform-Specific Influences on Vascular Disease.International journal of molecular sciences · 2026Article
- APOE4 Drives Uniquely Dysfunctional Human Microglial States in Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Microglia in systemic neuroimmune communication: functions beyond phagocytosis.Trends in immunology · 2026Review
- Sleep deprivation induces anxiety-like behaviors through IL-6 driven astrocyte-GABAergic neuron crosstalk in the PAG-ACC circuit.Journal of neuroinflammation · 2026Article
- Multiscale Approximations to Understand the Complex Role of Microglia in Alzheimer's Disease.The European journal of neuroscience · 2026Review
- A Question of Origins: Non-neuronal Sources of Amyloid-β.Neuroscience bulletin · 2026Review
- Abi3Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
29 authors at 7 institutions in 2 countries.
Funding
Abstract
Microglial involvement in Alzheimer's disease (AD) pathology has emerged as a risk-determining pathogenic event. While apolipoprotein E (APOE) is known to modify AD risk, it remains unclear how microglial apoE impacts brain cognition and AD pathology. Here, using conditional mouse models expressing apoE isoforms in microglia and central nervous system-associated macrophages (CAMs), we demonstrate a cell-autonomous effect of apoE3-mediated microglial activation and function, which are negated by apoE4. Expression of apoE3 in microglia/CAMs improves cognitive function, increases microglia surrounding amyloid plaque and reduces amyloid pathology and associated toxicity, whereas apoE4 expression either compromises or has no effects on these outcomes by impairing lipid metabolism. Single-cell transcriptomic profiling reveals increased antigen presentation and interferon pathways upon apoE3 expression. In contrast, apoE4 expression downregulates complement and lysosomal pathways, and promotes stress-related responses. Moreover, in the presence of mouse endogenous apoE, microglial apoE4 exacerbates amyloid pathology. Finally, we observed a reduction in Lgals3-positive responsive microglia surrounding amyloid plaque and an increased accumulation of lipid droplets in APOE4 human brains and induced pluripotent stem cell-derived microglia. Our findings establish critical isoform-dependent effects of microglia/CAM-expressed apoE in brain function and the development of amyloid pathology, providing new insight into how apoE4 vastly increases AD risk.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.