ArticleThe Journal of biological chemistry2015
Tau Trimers Are the Minimal Propagation Unit Spontaneously Internalized to Seed Intracellular Aggregation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 2 of them syntheses that pooled it.
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Who cites it
134 citing papers in PubMed, 2 syntheses or guidelines pooled it, 227 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
- The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD).International journal of molecular sciences · 2019Pooled it
- Alzheimer's disease: from molecular pathways to therapies.Molecular biomedicine · 2026Review
- Human Brain Contusions Contain Pathogenic Transmissible Species that Induce Progressive Cognitive Decline and Tau Pathology in Mice.Annals of neurology · 2026Article
- Tau conformation, distribution and PET imaging correlations in progressive supranuclear palsy.Translational neurodegeneration · 2026Review
- Regional correlates of tau pathology and synaptic function in primary age-related tauopathy.Journal of Alzheimer's disease : JAD · 2026Article
- Tau aggregation.Histology and histopathology · 2026Review
- Pretangle tau pathology accrual in the default mode network during the progression of Alzheimer's disease.Molecular neurodegeneration advances · 2026Article
- Early onset rapidly progressive frontotemporal dementia due to a novel MAPT P301A variant with functional validation of pathogenicity.NPJ dementia · 2026Article
- APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Seed structure and phosphorylation in the fuzzy coat impact tau seeding competency.Nature communications · 2025Article
- Cryo-EM structural analyses reveal diverse porous structures in brain-derived tau oligomers.Biochemical and biophysical research communications · 2025Article
- hiPSC-neurons recapitulate the subtype-specific cell intrinsic nature of susceptibility to neurodegenerative disease-relevant aggregation.Acta neuropathologica communications · 2025Article
- Inhibition of tau neuronal internalization using anti-tau single domain antibodies.Nature communications · 2025Article
- Functional classification of tauopathy strains reveals the role of protofilament core residues.Science advances · 2025Article
- Liposome nanoparticle conjugation and cell penetrating peptide sequences (CPPs) enhance the cellular delivery of the tau aggregation inhibitor RI-AG03.Journal of cellular and molecular medicine · 2024Article
- Hyperphosphorylated Tau Inflicts Intracellular Stress Responses that Are Mitigated by Apomorphine.Molecular neurobiology · 2024Article
- Precision proteoform design for 4R tau isoform selective templated aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
- Lymphocyte-Activation Gene 3 Facilitates Pathological Tau Neuron-to-Neuron Transmission.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
74 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
Tau amyloid assemblies propagate aggregation from the outside to the inside of a cell, which may mediate progression of the tauopathies. The critical size of Tau assemblies, or "seeds," responsible for this activity is currently unknown, but this could be important for the design of effective therapies. We studied recombinant Tau repeat domain (RD) and Tau assemblies purified from Alzheimer disease (AD) brain composed largely of full-length Tau. Large RD fibrils were first sonicated to create a range of assembly sizes. We confirmed our ability to resolve stable assemblies ranging from n = 1 to >100 units of Tau using size exclusion chromatography, fluorescence correlation spectroscopy, cross-linking followed by Western blot, and mass spectrometry. All recombinant Tau assemblies bound heparan sulfate proteoglycans on the cell surface, which are required for Tau uptake and seeding, because they were equivalently sensitive to inhibition by heparin and chlorate. However, cells only internalized RD assemblies of n ≥ 3 units. We next analyzed Tau assemblies from AD or control brains. AD brains contained aggregated species, whereas normal brains had predominantly monomer, and no evidence of large assemblies. HEK293 cells and primary neurons spontaneously internalized Tau of n ≥ 3 units from AD brain in a heparin- and chlorate-sensitive manner. Only n ≥ 3-unit assemblies from AD brain spontaneously seeded intracellular Tau aggregation in HEK293 cells. These results indicate that a clear minimum size (n = 3) of Tau seed exists for spontaneous propagation of Tau aggregation from the outside to the inside of a cell, whereas many larger sizes of soluble aggregates trigger uptake and seeding.
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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.