ArticleThe EMBO journal2015
Removing endogenous tau does not prevent tau propagation yet reduces its neurotoxicity.
Article in The EMBO journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 128 citations in OpenAlex.
- TDP-43 Aggregation: The Healthy-Toxic Balance of the Prion-Like Domain.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Loss of endogenous tau suppresses APOE4-induced patterned behavioral decline and axon dysmorphia in a model of Alzheimer's disease.Disease models & mechanisms · 2026Article
- Modification of early behavioural, physiological and neuropathological endpoints by syntaxin-6 knockout in a humanised P301S transgenic model of tauopathy.Acta neuropathologica · 2026Article
- Artificial microRNAs targeting tau enable post-symptomatic functional recovery in aged tauopathy mice.Molecular therapy. Nucleic acids · 2026Article
- Promoter mutagenesis and a massively parallel reporter screen of thebioRxiv : the preprint server for biology · 2026Article
- Connectivity as a universal predictor of tau progression in atypical Alzheimer's disease.Brain : a journal of neurology · 2025Article
- Low-dose radiation and malathion co-exposure instigates long-term neurological sequelae and synergistic disruption of lipid homeostasis and energy metabolism in the hippocampus.Scientific reports · 2025Article
- Molecular signatures of regional vulnerability to tauopathy in excitatory cortical neurons.Acta neuropathologica · 2025Article
- Alzheimer disease-associated tau post-translational modification mimics impact tau propagation and uptake.Journal of neuropathology and experimental neurology · 2025Article
- Hyperphosphorylated tau-based Alzheimer's Disease drug discovery: Identification of inhibitors of tau aggregation and cytotoxicity.SLAS discovery : advancing life sciences R & D · 2025Article
- The Impact of the Exposome on Alzheimer's Disease: The Influence of Nutrition.International journal of molecular sciences · 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
- A framework for translating tauopathy therapeutics: Drug discovery to clinical trials.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- Severe neurodegeneration in brains of transgenic rats producing human tau prions.Acta neuropathologica · 2024Article
- Chronic Neuronal Hyperexcitation Exacerbates Tau Propagation in a Mouse Model of Tauopathy.International journal of molecular sciences · 2024Article
- Metal Toxicity and Dementia Including Frontotemporal Dementia: Current State of Knowledge.Antioxidants (Basel, Switzerland) · 2024Review
- Effects of heterologous human tau protein expression in yeast models of proteotoxic stress response.CNS neuroscience & therapeutics · 2024Article
- The Role of Tau Pathology in Alzheimer's Disease and Down Syndrome.Journal of clinical medicine · 2024Review
- Neuronal MAPT expression is mediated by long-range interactions with cis-regulatory elements.American journal of human genetics · 2024Article
- Reevaluating tau reduction as a therapeutic approach for tauopathies: Insights and perspectives.Cytoskeleton (Hoboken, N.J.) · 2024Article
21 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
In Alzheimer's disease and tauopathies, tau protein aggregates into neurofibrillary tangles that progressively spread to synaptically connected brain regions. A prion-like mechanism has been suggested: misfolded tau propagating through the brain seeds neurotoxic aggregation of soluble tau in recipient neurons. We use transgenic mice and viral tau expression to test the hypotheses that trans-synaptic tau propagation, aggregation, and toxicity rely on the presence of endogenous soluble tau. Surprisingly, mice expressing human P301Ltau in the entorhinal cortex showed equivalent tau propagation and accumulation in recipient neurons even in the absence of endogenous tau. We then tested whether the lack of endogenous tau protects against misfolded tau aggregation and toxicity, a second prion model paradigm for tau, using P301Ltau-overexpressing mice with severe tangle pathology and neurodegeneration. Crossed onto tau-null background, these mice had similar tangle numbers but were protected against neurotoxicity. Therefore, misfolded tau can propagate across neural systems without requisite templated misfolding, but the absence of endogenous tau markedly blunts toxicity. These results show that tau does not strictly classify as a prion protein.
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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.