ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
CD14 and toll-like receptors 2 and 4 are required for fibrillar A{beta}-stimulated microglial activation.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 345 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
345 citing papers in PubMed, 3 syntheses or guidelines pooled it, 595 citations in OpenAlex.
- Role and Mechanism of Microglia in White Matter Injury Recovery in Ischemic Stroke.Immunity, inflammation and disease · 2025Pooled it
- The Key Drivers of Brain Injury by Systemic Inflammatory Responses after Sepsis: Microglia and Neuroinflammation.Molecular neurobiology · 2023Pooled it
- How Periodontitis or Periodontal Bacteria Can Influence Alzheimer's Disease Features? A Systematic Review of Pre-Clinical Studies.Journal of Alzheimer's disease : JAD · 2023Pooled it
- Mechanisms of Brain Aging and Their Links to Alzheimer's and Parkinson's Disease Pathology.International journal of molecular sciences · 2026Review
- Sleep Deprivation and Neuronal Hyperexcitation Share Transcriptomic Signatures.Neuropsychopharmacology reports · 2026Article
- TDP-43-immunity-microbiota axis in amyotrophic lateral sclerosis: A potential pathogenic mechanism.Neural regeneration research · 2026Article
- Review
- Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Review
- Alpha-Ketoglutarate: A Metabolic Regulator of Cellular Homeostasis and Pathophysiology.Biomedicines · 2026Review
- HLA-DRB1*15:01 drives sex- and age-dependent microglial activation and neuroimmune signaling.bioRxiv : the preprint server for biology · 2026Article
- Inflammatory stimulus enhances synaptic material uptake by adult APP microglia in a microfluidic neuron-microglia co-culture model.Journal of neuroinflammation · 2026Article
- Selective vulnerability of the aging cholinergic system to amyloid pathology revealed by induced APP overexpression.Journal of neuroinflammation · 2026Article
- Microglia-mediated neuroinflammation in Alzheimer's disease: mechanisms and emerging therapeutic targets.Frontiers in cellular neuroscience · 2026Review
- HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling.Frontiers in immunology · 2026Article
- Ginsenoside Re mitigates AβJournal of ginseng research · 2026Article
- Direct toll-like receptor 4 inhibition in Alzheimer's disease models: a focused scoping review of inflammatory, amyloid-handling, and functional outcomes.Frontiers in aging neuroscience · 2026Review
- Taking its TOLL: the role of toll-like receptor 4 in human health and disease, and its potential as a therapeutic target.Frontiers in immunology · 2026Review
- Neuroimmune Dysregulation and AI-Driven Therapeutic Strategies in Alzheimer's Disease.Cellular and molecular neurobiology · 2025Review
- Identification and validation of microglia-associated genes in ischemic stroke using single-cell and bulk RNA-seq.Molecular brain · 2025Article
285 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
4 authors at 3 institutions in 1 country.
Funding
Abstract
Microglia are the brain's tissue macrophages and are found in an activated state surrounding beta-amyloid plaques in the Alzheimer's disease brain. Microglia interact with fibrillar beta-amyloid (fAbeta) through an ensemble of surface receptors composed of the alpha(6)beta(1) integrin, CD36, CD47, and the class A scavenger receptor. These receptors act in concert to initiate intracellular signaling cascades and phenotypic activation of these cells. However, it is unclear how engagement of this receptor complex is linked to the induction of an activated microglial phenotype. We report that the response of microglial cells to fibrillar forms of Abeta requires the participation of Toll-like receptors (TLRs) and the coreceptor CD14. The response of microglia to fAbeta is reliant upon CD14, which act together with TLR4 and TLR2 to bind fAbeta and to activate intracellular signaling. We find that cells lacking these receptors could not initiate a Src-Vav-Rac signaling cascade leading to reactive oxygen species production and phagocytosis. The fAbeta-mediated activation of p38 MAPK also required CD14, TLR4, and TLR2. Inhibition of p38 abrogated fAbeta-induced reactive oxygen species production and attenuated the induction of phagocytosis. Microglia lacking CD14, TLR4, and TLR2 showed no induction of phosphorylated IkappaBalpha following fAbeta. These data indicate these innate immune receptors function as members of the microglial fAbeta receptor complex and identify the signaling mechanisms whereby they contribute to microglial activation.
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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.