ArticleNature communications2022
Hyperphosphorylated tau self-assembles into amorphous aggregates eliciting TLR4-dependent responses.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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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.
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Who cites it
47 citing papers in PubMed, 72 citations in OpenAlex.
- Site-specific phosphorylation of Ser352 drives aggregation of Tau R4 under acidosis conditions.Chemical science · 2026Article
- Tau Aggregate Imaging and Transcriptomics of Alzheimer's Disease Brain at Different Stages of Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Visceral adipose tissue differentially affects tau and Aβ pathology in 3xTg-AD mice.Cell communication and signaling : CCS · 2026Article
- A Dual-Emissive Organoplatinum(II) Probe Enables Ratiometric NIR and Phosphorescence Lifetime Imaging of Cell Membrane Integrity.Chemical & biomedical imaging · 2026Article
- Mesenchymal stromal cells and neuroinflammation: a multimodal approach to neuroprotection and future therapeutic horizons.Translational neurodegeneration · 2026Review
- PROTAC-mediated multi-target protein degradation in Alzheimer's disease: mechanistic insights, therapeutic applications, and translational challenges.RSC medicinal chemistry · 2026Review
- Type-1 interferons associated with microglial-mediated neuroinflammation in Alzheimer's disease.Journal of neuroinflammation · 2026Review
- Methods for studying the effects of phosphorylation patterns in proteins.Biochemical Society transactions · 2026Review
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- The Neurogenic Niche: Interactions Among Vessels, Glia, and Neural Stem Cells.Stem cells international · 2026Review
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Single-Oligomer Characterization of Tau Phosphorylation and Mechanical State.ACS measurement science au · 2025Article
- Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency.Nature communications · 2025Article
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Listerin Alleviates Alzheimer's Disease through IRE1-mediated Decay of TLR4 mRNA.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Astrocyte-driven vasoconstriction impairs glymphatic clearance in a human tauopathy-on-chip model.APL bioengineering · 2025Article
- Cellular and molecular mechanisms of pathological tau phosphorylation in traumatic brain injury: implications for chronic traumatic encephalopathy.Molecular neurodegeneration · 2025Review
- The potential of novel gut microbiota supplement in mitigating gut inflammation, alleviating oxidative stress linked to aging, and improving cognitive function in aged mice.BMC complementary medicine and therapies · 2025Article
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 1 country.
Funding
Abstract
Soluble aggregates of the microtubule-associated protein tau have been challenging to assemble and characterize, despite their important role in the development of tauopathies. We found that sequential hyperphosphorylation by protein kinase A in conjugation with either glycogen synthase kinase 3β or stress activated protein kinase 4 enabled recombinant wild-type tau of isoform 0N4R to spontaneously polymerize into small amorphous aggregates in vitro. We employed tandem mass spectrometry to determine the phosphorylation sites, high-resolution native mass spectrometry to measure the degree of phosphorylation, and super-resolution microscopy and electron microscopy to characterize the morphology of aggregates formed. Functionally, compared with the unmodified aggregates, which require heparin induction to assemble, these self-assembled hyperphosphorylated tau aggregates more efficiently disrupt membrane bilayers and induce Toll-like receptor 4-dependent responses in human macrophages. Together, our results demonstrate that hyperphosphorylated tau aggregates are potentially damaging to cells, suggesting a mechanism for how hyperphosphorylation could drive neuroinflammation in tauopathies.
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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.