ArticleFrontiers in neurology2013
Are tau aggregates toxic or protective in tauopathies?
Article in Frontiers in neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 123 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
123 citing papers in PubMed, 1 synthesis or guideline pooled it, 207 citations in OpenAlex.
- The Role of Protein Misfolding and Tau Oligomers (TauOs) in Alzheimer's Disease (AD).International journal of molecular sciences · 2019Pooled it
- Recent advances of dual PROTACs for potential therapeutic applications.Molecular diversity · 2026Review
- Tau physiology and pathology: impacts on cellular structures and neurodegenerative diseases.Inflammopharmacology · 2026Review
- A Virus-Like-Particle-Based Conjugate Vaccine Targeting the Microtubule Binding Region of Tau Protein.ACS omega · 2026Article
- FKBP51 inhibition by SAFit2 modulates tau pathology and cognitive deficits in PS19 mice.Alzheimer's research & therapy · 2026Article
- Tau oligomerization induces nuclear lamina invagination and chromatin remodeling in Alzheimer's disease.Acta neuropathologica · 2026Article
- A distinct tau oligomer strain defines the molecular and proteomic landscape of rapidly progressive Alzheimer's disease.Acta neuropathologica · 2026Article
- Investigating the role of EFhd2 protein in modulating tau pathology in a tauopathy mouse model.Frontiers in molecular neuroscience · 2026Article
- Neuronal gene profiling of tau oligomer-bearing cholinergic nucleus basalis neurons during the onset of Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Phosphorylation at serine 214 correlates with tau seeding activity in an age-dependent manner in two mouse models for tauopathies and is required for tau transsynaptic propagation.Journal of Alzheimer's disease : JAD · 2025Article
- Emerging roles for innate and adaptive immunity in tauopathies.Cell reports · 2025Review
- Tau Oligomers in Alzheimer's Disease: Modulation Effect of Osmolytes on Amplified Brain-Derived Tau Oligomers.ACS chemical neuroscience · 2025Article
- A brain-derived tau oligomer polymorph is associated with cognitive resilience to Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- ApoE3 Christchurch and tau interaction as a protective mechanism against Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro.The Biochemical journal · 2025Article
- Functional Analysis of Direct In Vitro Effect of Phosphorylated Tau on Mitochondrial Respiration and Hydrogen Peroxide Production.Biomolecules · 2025Article
- Extracellular PHF-tau modulates astrocyte mitochondrial dynamics and mediates neuronal connectivity.Translational neurodegeneration · 2025Article
- Uncovering α-synuclein and tau burden in Alzheimer's and Lewy body diseases.Brain communications · 2025Article
- All-Trans Retinoic Acid-Induced Cell Surface Heat Shock Protein 90 Mediates Tau Protein Internalization and Degradation in Human Microglia.Molecular neurobiology · 2025Article
- Therapeutic Potential of Traditional Oriental Medicines in Targeting Tau Pathology: Insights from Cell-free and Cell-based Screening.Current medicinal chemistry · 2025Article
63 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation of highly phosphorylated tau into aggregated forms such as filaments and neurofibrillary tangles is one of the defining pathological hallmarks of Alzheimer's disease and other tauopathies. Hence therapeutic strategies have focused on inhibition of tau phosphorylation or disruption of aggregation. However, animal models imply that tau-mediated dysfunction and toxicity do not require aggregation but instead are caused by soluble hyper-phosphorylated tau. Over the years, our findings from a Drosophila model of tauopathy have reinforced this. We have shown that highly phosphorylated wild-type human tau causes behavioral deficits resulting from synaptic dysfunction, axonal transport disruption, and cytoskeletal destabilization in vivo. These deficits are evident in the absence of neuronal death or filament/tangle formation. Unsurprisingly, both pharmacological and genetic inhibition of GSK-3β rescue these tau phenotypes. However, GSK-3β inhibition also unexpectedly increases tau protein levels, and produces insoluble granular tau oligomers. As well as underlining the growing consensus that tau toxicity is mediated by a highly phosphorylated soluble tau species, our findings further show that not all insoluble tau aggregates are toxic. Some tau aggregates, in particular tau oligomers, are non-toxic, and may even be protective against tau toxicity in vivo. This has serious implications for emerging therapeutic strategies to dissolve tau aggregates, which might be ineffective or even counter-productive. In light of this, it is imperative to identify the key toxic tau species and to understand how it mediates dysfunction and degeneration so that the effective disease-modifying therapies can be developed.
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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.