ArticleNature communications2021
Phospholipids of APOE lipoproteins activate microglia in an isoform-specific manner in preclinical models of Alzheimer's disease.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.Acta neuropathologica · 2022Pooled it
- Review
- APOEε4 attenuates early TREM2-mediated microglial responses and influences disease trajectories in dementia with Lewy bodies.Research square · 2026Article
- ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer's disease and related disorders.Molecular neurodegeneration · 2026Review
- Microglia and neuroinflammation: function, heterogeneity, and crosstalk.Cellular & molecular immunology · 2026Review
- Plasma GDF15 affects long-term dementia risk and alters neuroimmune signaling.Science advances · 2026Article
- Integration of Transcriptional Signatures from Brain Tissue and Plasma Extracellular Vesicles of a Preclinical Tauopathy Mouse Model.International journal of molecular sciences · 2026Article
- The Effect of Metabolic Syndrome on Alzheimer's Disease: Physical Activity as a Preventive and Therapeutic Measure.Brain sciences · 2026Review
- Scalable discovery of spatial multicellular patterns via neighborhood-to-sequence transformation.Communications biology · 2026Article
- Alzheimer's Disease: From Pathogenesis to Emerging Therapeutic Targets.Journal of clinical medicine · 2026Review
- Amyloid-Frontiers in neuroscience · 2026Review
- Plasmalogen deficiency and the Alzheimer's disease risk of apolipoprotein E4.Brain communications · 2026Article
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- APOE4 to APOE2 allelic switching in mice improves Alzheimer's disease-related metabolic signatures, neuropathology and cognition.Nature neuroscience · 2025Article
- The Janus face of CaMKII: from memory consolidation to neurotoxic switch in Alzheimer's disease.Archives of toxicology · 2025Review
- Microglia-Mediated Phagocytosis in Alzheimer's Disease: Mechanisms, Heterogeneity, and Therapeutic Insights.Biomolecules · 2025Review
- The Synergistic Role of ApoE4 and GSK3β in Alzheimer's Disease: Pathological Mechanisms and Therapeutic Implications.Molecular neurobiology · 2025Review
- Abnormal behaviors and glial responses in an animal model of tau pathology.Molecular brain · 2025Article
- Mechanisms of high-density lipoprotein in regulating blood-brain barrier function: insights and implications.Fluids and barriers of the CNS · 2025Review
31 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
13 authors at 1 institution in 1 country.
Funding
Abstract
APOE and Trem2 are major genetic risk factors for Alzheimer's disease (AD), but how they affect microglia response to Aβ remains unclear. Here we report an APOE isoform-specific phospholipid signature with correlation between human APOEε3/3 and APOEε4/4 AD brain and lipoproteins from astrocyte conditioned media of APOE3 and APOE4 mice. Using preclinical AD mouse models, we show that APOE3 lipoproteins, unlike APOE4, induce faster microglial migration towards injected Aβ, facilitate Aβ uptake, and ameliorate Aβ effects on cognition. Bulk and single-cell RNA-seq demonstrate that, compared to APOE4, cortical infusion of APOE3 lipoproteins upregulates a higher proportion of genes linked to an activated microglia response, and this trend is augmented by TREM2 deficiency. In vitro, lack of TREM2 decreases Aβ uptake by APOE4-treated microglia only, suggesting TREM2-APOE interaction. Our study elucidates phenotypic and transcriptional differences in microglial response to Aβ mediated by APOE3 or APOE4 lipoproteins in preclinical models of AD.
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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.