ArticleThe Journal of biological chemistry2013
Small misfolded Tau species are internalized via bulk endocytosis and anterogradely and retrogradely transported in neurons.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 305 papers, 1 of them a synthesis that pooled it.
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Who cites it
305 citing papers in PubMed, 1 synthesis or guideline pooled it, 541 citations in OpenAlex.
- Shaping the future of preclinical development of successful disease-modifying drugs against Alzheimer's disease: a systematic review of tau propagation models.Acta neuropathologica communications · 2024Pooled it
- Assessment of Efficacy and Safety of Zagotenemab: Results From PERISCOPE-ALZ, a Phase 2 Study in Early Symptomatic Alzheimer Disease.Neurology · 2024Trial
- Tau-targeting antisense oligonucleotide MAPTNature medicine · 2023Trial
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- Limited Detectability of Network Functional Alterations in a Tauopathy Model Using Mouse Primary Cortical Cultures.Biomedicines · 2026Article
- Article
- Tau seeds induce neurofibrillary tangle formation across brain regions via individual-specific connectivity.Neuron · 2026Article
- Reducing PI4KIIIα Levels or Activity Limits Tau Seed Internalization and Assembly in Human Cortical Neurons.Cells · 2026Article
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Aberrant tau accumulation caused by MAPT mutations induces early pathological changes in axonal transport that are rescued by p38α inhibition.Nature neuroscience · 2026Article
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Structural and mechanistic characterization of heparin interactions with tau fibrils.The Journal of biological chemistry · 2026Article
- Article
- Amyloid-mediated RNA uptake by sperm for embryonic delivery.bioRxiv : the preprint server for biology · 2025Article
- Common Mechanism Underlying Synaptic Dysfunction Caused by Preformed Fibril-Induced Accumulation of α-Synuclein or Tau in a Culture Propagation Model.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency.Nature communications · 2025Article
- Cortical circuit principles predict patterns of trauma induced tauopathy in humans.Cerebral cortex (New York, N.Y. : 1991) · 2025Article
- Dysregulation of Inositol Polyphosphate 5-Phosphatase OCRL in Alzheimer's Disease: Implications for Autophagy Dysfunction.International journal of molecular sciences · 2025Article
- hiPSC-neurons recapitulate the subtype-specific cell intrinsic nature of susceptibility to neurodegenerative disease-relevant aggregation.Acta neuropathologica communications · 2025Article
- Directionality bias underpins divergent spatiotemporal progression of Alzheimer-related tauopathy in mouse models.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
245 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
The accumulation of Tau into aggregates is associated with key pathological events in frontotemporal lobe degeneration (FTD-Tau) and Alzheimer disease (AD). Recent data have shown that misfolded Tau can be internalized by cells in vitro (Frost, B., Jacks, R. L., and Diamond, M. I. (2009) J. Biol. Chem. 284, 12845-12852) and propagate pathology in vivo (Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., Jucker, M., Goedert, M., and Tolnay, M. (2009) Nat. Cell Biol. 11, 909-913; Lasagna-Reeves, C. A., Castillo-Carranza, D. L., Sengupta, U., Guerrero-Munoz, M. J., Kiritoshi, T., Neugebauer, V., Jackson, G. R., and Kayed, R. (2012) Sci. Rep. 2, 700). Here we show that recombinant Tau misfolds into low molecular weight (LMW) aggregates prior to assembly into fibrils, and both extracellular LMW Tau aggregates and short fibrils, but not monomers, long fibrils, nor long filaments purified from brain extract are taken up by neurons. Remarkably, misfolded Tau can be internalized at the somatodendritic compartment, or the axon terminals and it can be transported anterogradely, retrogradely, and can enhance tauopathy in vivo. The internalized Tau aggregates co-localize with dextran, a bulk-endocytosis marker, and with the endolysosomal compartments. Our findings demonstrate that exogenous Tau can be taken up by cells, uptake depends on both the conformation and size of the Tau aggregates and once inside cells, Tau can be transported. These data provide support for observations that tauopathy can spread trans-synaptically in vivo, via cell-to-cell transfer.
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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.