ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Lentiviral delivery of the human wild-type tau protein mediates a slow and progressive neurodegenerative tau pathology in the rat brain.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 36 citations in OpenAlex.
- Amplification of seeding-competent tau aggregates by PMCA in human and experimental tauopathies.Acta neuropathologica communications · 2026Article
- N-terminally acetylated Met11-Tau: a new pathological truncated Tau species with functional relevance in Alzheimer's disease.Translational neurodegeneration · 2026Article
- Anti-tau VHH therapy against PHF6: a safe approach to slowing the phenotype of tau pathology.Alzheimer's research & therapy · 2025Article
- Modeling Alzheimer's Disease: A Review of Gene-Modified and Induced Animal Models, Complex Cell Culture Models, and Computational Modeling.Brain sciences · 2025Review
- Developing and optimizing a biocompatible tauopathy model using extracellular vesicle-mediated gene delivery.Frontiers in medicine · 2025Article
- Anterograde and Retrograde Propagation of Inoculated Human Tau Fibrils and Tau Oligomers in a Non-Transgenic Rat Tauopathy Model.Biomedicines · 2023Article
- Article
- Towards a Mechanistic Model of Tau-Mediated Pathology in Tauopathies: What Can We Learn from Cell-Based In Vitro Assays?International journal of molecular sciences · 2022Review
- Human wildtype tau expression in cholinergic pedunculopontine tegmental neurons is sufficient to produce PSP-like behavioural deficits and neuropathology.The European journal of neuroscience · 2021Article
- From the prion-like propagation hypothesis to therapeutic strategies of anti-tau immunotherapy.Acta neuropathologica · 2020Review
- Encephalopathy induced by Alzheimer brain inoculation in a non-human primate.Acta neuropathologica communications · 2019Article
- Neuronal AMP-activated protein kinase hyper-activation induces synaptic loss by an autophagy-mediated process.Cell death & disease · 2019Article
- Spreading of α-Synuclein and Tau: A Systematic Comparison of the Mechanisms Involved.Frontiers in molecular neuroscience · 2019Review
- Different tau species lead to heterogeneous tau pathology propagation and misfolding.Acta neuropathologica communications · 2018Article
- Potentiating tangle formation reduces acute toxicity of soluble tau species in the rat.Brain : a journal of neurology · 2018Article
- Practical considerations for choosing a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2017Review
- Tau-mediated Neurodegeneration and Potential Implications in Diagnosis and Treatment of Alzheimer's Disease.Chinese medical journal · 2017Review
- Axonal Degeneration in Tauopathies: Disease Relevance and Underlying Mechanisms.Frontiers in neuroscience · 2017Review
- Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.Acta neuropathologica communications · 2016Article
- Neuronal activity enhances tau propagation and tau pathology in vivo.Nature neuroscience · 2016Article
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Authors and funding
14 authors at 8 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Most models for tauopathy use a mutated form of the Tau gene, MAPT, that is found in frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17) and that leads to rapid neurofibrillary degeneration (NFD). Use of a wild-type (WT) form of human Tau protein to model the aggregation and associated neurodegenerative processes of Tau in the mouse brain has thus far been unsuccessful. In the present study, we generated an original "sporadic tauopathy-like" model in the rat hippocampus, encoding six Tau isoforms as found in humans, using lentiviral vectors (LVs) for the delivery of a human WT Tau. The overexpression of human WT Tau in pyramidal neurons resulted in NFD, the morphological characteristics and kinetics of which reflected the slow and sporadic neurodegenerative processes observed in sporadic tauopathies, unlike the rapid neurodegenerative processes leading to cell death and ghost tangles triggered by the FTDP-17 mutant Tau P301L. This new model highlights differences in the molecular and cellular mechanisms underlying the pathological processes induced by WT and mutant Tau and suggests that preference should be given to animal models using WT Tau in the quest to understand sporadic tauopathies.
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