ArticleActa neuropathologica2021
In vitro amplification of pathogenic tau conserves disease-specific bioactive characteristics.
Article in Acta neuropathologica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
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Who cites it
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 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
- Article
- Conformation-specific monoclonal antibodies reveal early Tau structural intermediates in Alzheimer's disease.The Journal of biological chemistry · 2026Article
- Heterogeneous Dynamics of the Fuzzy Coat of Full-Length Phospho-Mimetic Tau Fibrils.Journal of the American Chemical Society · 2026Article
- ACSS2 upregulation enhances neuronal resilience to aging and tau-associated neurodegeneration.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Refining a mouse model of progressive supranuclear palsy through inoculation of human post-mortem brain-derived tau.BMC research notes · 2026Article
- 4R-tau seeding activity reveals molecular subtypes in progressive supranuclear palsy.Nature communications · 2025Article
- APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- A Novel Spectral Barcoding and Classification Approach for Complex Biological Samples Using Multiexcitation Raman Spectroscopy (MX-Raman).Analytical chemistry · 2025Article
- Lysosomes as Dynamic Regulators of Metabolic Signaling and Organ Physiology in Aging: From Mechanism to Therapy.Aging and disease · 2025Review
- Limitations and Applications of Rodent Models in Tauopathy and Synucleinopathy Research.Journal of neurochemistry · 2025Review
- Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- Inhibition of autophagosome-lysosome fusion contributes to TDCIPP-induced Aβ1-42 production in N2a-APPswe cells.Heliyon · 2024Article
- MSUT2 regulates tau spreading via adenosinergic signaling mediated ASAP1 pathway in neurons.Acta neuropathologica · 2024Article
- Reduced progranulin increases tau and α-synuclein inclusions and alters mouse tauopathy phenotypes via glucocerebrosidase.Nature communications · 2024Article
- Neurodegenerative Disease Tauopathies.Annual review of pathology · 2024Review
- Toward an animal model of Progressive Supranuclear Palsy.Frontiers in neuroscience · 2024Review
- β-Bracelets: Macrocyclic Cross-β Epitope Mimics Based on a Tau Conformational Strain.Journal of the American Chemical Society · 2023Article
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
The microtubule-associated protein tau (tau) forms hyperphosphorylated aggregates in the brains of tauopathy patients that can be pathologically and biochemically defined as distinct tau strains. Recent studies show that these tau strains exhibit strain-specific biological activities, also referred to as pathogenicities, in the tau spreading models. Currently, the specific pathogenicity of human-derived tau strains cannot be fully recapitulated by synthetic tau preformed fibrils (pffs), which are generated from recombinant tau protein. Reproducing disease-relevant tau pathology in cell and animal models necessitates the use of human brain-derived tau seeds. However, the availability of human-derived tau is extremely limited. Generation of tau variants that can mimic the pathogenicity of human-derived tau seeds would significantly extend the scale of experimental design within the field of tauopathy research. Previous studies have demonstrated that in vitro seeding reactions can amplify the beta-sheet structure of tau protein from a minute quantity of human-derived tau. However, whether the strain-specific pathogenicities of the original, human-derived tau seeds are conserved in the amplified tau strains has yet to be experimentally validated. Here, we used biochemically enriched brain-derived tau seeds from Alzheimer's disease (AD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) patient brains with a modified seeding protocol to template the recruitment of recombinant 2N4R (T40) tau in vitro. We quantitatively interrogated efficacy of the amplification reactions and the pathogenic fidelity of the amplified material to the original tau seeds using recently developed sporadic tau spreading models. Our data suggest that different tau strains can be faithfully amplified in vitro from tau isolated from different tauopathy brains and that the amplified tau variants retain their strain-dependent pathogenic characteristics.
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