ArticleThe Journal of biological chemistry2012
Trans-cellular propagation of Tau aggregation by fibrillar species.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 325 papers.
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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.
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Who cites it
325 citing papers in PubMed, 554 citations in OpenAlex.
- When Pathologies Collide: The Intersection of Tau and Alpha-Synuclein in Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Tau Disaggregation by a CNS-Permeable Small Molecule Reduces Fibril and Oligomer Burden and Preserves Proteostasis and Behavior.bioRxiv : the preprint server for biology · 2026Article
- Loss of endogenous tau suppresses APOE4-induced patterned behavioral decline and axon dysmorphia in a model of Alzheimer's disease.Disease models & mechanisms · 2026Article
- Tracking tau and cellular responses in human iPSC-microglia: from uptake to seedable secretion, including in extracellular vesicles.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Timing matters: early administration of a high-affinity antibody targeting the tau repeat domain prevents aggregation in a mouse tauopathy model.Alzheimer's research & therapy · 2026Article
- Cathepsin-dependent amyloid formation drives mechanical rupture of lysosomal membranes.bioRxiv : the preprint server for biology · 2026Article
- APP E590D mutation increases generation of Aβ and Aη peptides and exacerbates tauopathy.NPJ dementia · 2026Article
- A high-throughput drug screening assay for anti-tau aggregation using split GFP and flow cytometry.Scientific reports · 2025Article
- Intercellular propagation of RIPK1/RIPK3 amyloid fibrils.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Immunization targeting diseased proteins in synucleinopathy and tauopathy: insights from clinical trials.Translational neurodegeneration · 2025Review
- Alzheimer disease-associated tau post-translational modification mimics impact tau propagation and uptake.Journal of neuropathology and experimental neurology · 2025Article
- Macrocyclic β-arch peptides that mimic the structure and function of disease-associated tau folds.Nature chemistry · 2025Article
- Water-directed pinning is key to tau prion formation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multimodal spatial gradients to explain regional susceptibility to fibrillar tau in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Plant-Based Inhibitors of Protein Aggregation.Biomolecules · 2025Review
- PseudoSorter: A self-supervised spike sorting approach applied to reveal Tau-induced reductions in neuronal activity.Science advances · 2025Article
- Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer's disease.Acta neuropathologica communications · 2025Article
- "Proteinjury": a universal pathological mechanism mediated by cerebrospinal fluid in neurodegeneration and trauma.Frontiers in cell and developmental biology · 2025Review
- Prion and "Prion-Like" Detection: From Conventional Methods to Microfluidics or Lab-on-Chip Platforms to Monitor Seeding and Spreading of Misfolded Proteins.Sub-cellular biochemistry · 2025Review
- Microglial APOE3 Christchurch protects neurons from Tau pathology in a human iPSC-based model of Alzheimer's disease.Cell reports · 2024Article
265 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Aggregation of the microtubule associated protein Tau is associated with several neurodegenerative disorders, including Alzheimer disease and frontotemporal dementia. In Alzheimer disease, Tau pathology spreads progressively throughout the brain, possibly along existing neural networks. However, it is still unclear how the propagation of Tau misfolding occurs. Intriguingly, in animal models, vaccine-based therapies have reduced Tau and synuclein pathology by uncertain mechanisms, given that these proteins are intracellular. We have previously speculated that trans-cellular propagation of misfolding could be mediated by a process similar to prion pathogenesis, in which fibrillar Tau aggregates spread pathology from cell to cell. However, there has been little evidence to demonstrate true trans-cellular propagation of Tau misfolding, in which Tau aggregates from one cell directly contact Tau protein in the recipient cell to trigger further aggregation. Here we have observed that intracellular Tau fibrils are directly released into the medium and then taken up by co-cultured cells. Internalized Tau aggregates induce fibrillization of intracellular Tau in these naive recipient cells via direct protein-protein contact that we demonstrate using FRET. Tau aggregation can be amplified across several generations of cells. An anti-Tau monoclonal antibody blocks Tau aggregate propagation by trapping fibrils in the extracellular space and preventing their uptake. Thus, propagation of Tau protein misfolding among cells can be mediated by release and subsequent uptake of fibrils that directly contact native protein in recipient cells. These results support the model of aggregate propagation by templated conformational change and suggest a mechanism for vaccine-based therapies in neurodegenerative diseases.
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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.