ArticleThe Journal of clinical investigation2023
Tau fibrils induce glial inflammation and neuropathology via TLR2 in Alzheimer's disease-related mouse models.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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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
64 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The impact of physical exercise on neuroinflammation mechanism in Alzheimer's disease.Frontiers in aging neuroscience · 2024Pooled it
- Targeting innovative therapeutic approaches to the hallmarks of aging to combat Alzheimer's disease.Neural regeneration research · 2026Article
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Selective inhibition of TLR2 stimulates the maturation of oligodendroglial progenitor cells to oligodendrocytes.NeuroImmune pharmacology and therapeutics · 2026Article
- 10,11-Dehydrocurvularin attenuates LPS-induced neuroinflammation in BV2 cells by inhibiting the TLR2/MyD88/NLRP3 signaling pathway.Biochemistry and biophysics reports · 2026Article
- RNA-based therapeutics for Alzheimer's disease and related tauopathies: challenges and opportunities.The journal of prevention of Alzheimer's disease · 2026Review
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Magnesium Status in Celiac Disease: Potential Links with Neuroinflammatory Pathways and Gut-Brain Axis Dysfunction.International journal of molecular sciences · 2026Review
- Protein kinase CK2α' as a dual modulator of neuroimmune signaling and synaptic dysfunction in tauopathy.Translational neurodegeneration · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- MicroRNA and Alzheimer's disease: Diagnostic biomarkers and potential therapeutic targets.Neural regeneration research · 2026Article
- The Biological Basis, Mechanisms of Action, and Optimization Strategies of Exosomes Derived from Mesenchymal Stem Cells for the Treatment of Alzheimer's Disease.Molecular neurobiology · 2026Review
- Review
- Integration of Transcriptional Signatures from Brain Tissue and Plasma Extracellular Vesicles of a Preclinical Tauopathy Mouse Model.International journal of molecular sciences · 2026Article
- Dissecting Alzheimer's disease heterogeneity by cross-trait polygenic prediction.bioRxiv : the preprint server for biology · 2026Article
- PLGA Nanoparticle-based Anti-TLR2 scFv Gene Delivery for the Treatment of Alzheimer's Disease.Experimental neurobiology · 2026Article
- Immune signaling and function in neurodegeneration.The Journal of clinical investigation · 2026Review
- L-Leucine Upregulates Lysosomal Biogenesis and Autophagy to Lower Plaques in 5XFAD Mouse Model of Alzheimer's Disease.Journal of neurochemistry · 2026Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
Glial activation and inflammation coincide with neurofibrillary tangle (NFT) formation in neurons. However, the mechanism behind the interaction between tau fibrils and glia is poorly understood. Here, we found that tau preformed fibrils (PFFs) caused induction of inflammation in microglia by specifically activating the TLR2/MyD88, but not the TLR4/MyD88, pathway. Accordingly, the WT TLR2-interacting domain of MyD88 (wtTIDM) peptide inhibited tau PFF-induced activation of the TLR2/MyD88/NF-κB pathway, resulting in reduced inflammation. Nasal administration of wtTIDM in P301S tau-expressing PS19 mice was found to inhibit gliosis and inflammatory markers, as well as to reduce pathogenic tau in the hippocampus, resulting in improved cognitive behavior in PS19 mice. The inhibitory effect of wtTIDM on tau pathology was absent in PS19 mice lacking TLR2, reinforcing the essential involvement of TLR2 in wtTIDM-mediated effects in vivo. Studying the mechanism further, we found that the tau promoter harbored a potential NF-κB-binding site and that proinflammatory molecules increased transcription of tau in neurons via NF-κB. These results suggest that tau-induced neuroinflammation and neuropathology require TLR2 and that neuroinflammation directly upregulates tau in neurons via NF-κB, highlighting a direct connection between inflammation and tauopathy.
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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 Socratic graph.