ArticleActa neuropathologica2021
Photodynamic studies reveal rapid formation and appreciable turnover of tau inclusions.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- Temporal Trajectories of the Tau Aggregate Interactome Reveal Stage-Specific Vulnerabilities in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regional correlates of tau pathology and synaptic function in primary age-related tauopathy.Journal of Alzheimer's disease : JAD · 2026Article
- Confirmation of p-tau Ser356's association with Alzheimer's disease pathology and lowering in response to WZ4003 treatment in brain slice cultures. Reply to: "Phospho-tau Ser356 is mostly confined to pre-NFT neurons in Alzheimer's pathology".Acta neuropathologica · 2025Article
- Co-opting templated aggregation to degrade pathogenic tau assemblies and improve motor function.Cell · 2024Article
- Considerations for biomarker strategies in clinical trials investigating tau-targeting therapeutics for Alzheimer's disease.Translational neurodegeneration · 2024Review
- Involvement of the glymphatic/meningeal lymphatic system in Alzheimer's disease: insights into proteostasis and future directions.Cellular and molecular life sciences : CMLS · 2024Review
- Transgenic Dendra2::tau expression allows in vivo monitoring of tau proteostasis in Caenorhabditis elegans.Disease models & mechanisms · 2024Article
- Change in Cerebrospinal Fluid Tau Microtubule Binding Region Detects Symptom Onset, Cognitive Decline, Tangles, and Atrophy in Dominantly Inherited Alzheimer's Disease.Annals of neurology · 2023Article
- Intraneuronal tau aggregation induces the integrated stress response in astrocytes.Journal of molecular cell biology · 2023Article
- Optical pulse labeling studies reveal exogenous seeding slows α-synuclein clearance.NPJ Parkinson's disease · 2022Article
- Cortical waste clearance in normal and restricted sleep with potential runaway tau buildup in Alzheimer's disease.Scientific reports · 2022Article
- Pathogenic tau recruits wild-type tau into brain inclusions and induces gut degeneration in transgenic SPAM mice.Communications biology · 2022Article
- Parallel gold enhancement of quantum dots 565/655 for double-labelling correlative light and electron microscopy on human autopsied samples.Scientific reports · 2022Article
- Does Data-Independent Acquisition Data Contain Hidden Gems? A Case Study Related to Alzheimer's Disease.Journal of proteome research · 2022Article
- Disease-Modifying Therapies for Alzheimer's Disease: More Questions than Answers.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Tau Seeding Mouse Models with Patient Brain-Derived Aggregates.International journal of molecular sciences · 2021Review
- Tau isoforms are differentially expressed across the hippocampus in chronic traumatic encephalopathy and Alzheimer's disease.Acta neuropathologica communications · 2021Article
- Tau inclusion turnover could be a target.Nature reviews. Neurology · 2021Article
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12 authors at 2 institutions in 2 countries.
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Abstract
Accumulation of the tau protein in fibrillar intracellular aggregates is a defining feature of multiple neurodegenerative diseases collectively referred to as tauopathies. Despite intensive study of tau, there is limited information on the formation and clearance dynamics of tau inclusions. Using rAAV vectors to mediate expression of Dendra2-tagged human wild-type, P301L and pro-aggregant P301L/S320F tau proteins, with and without the addition of exogenous tau fibrillar seeds, we evaluated tau inclusion dynamics in organotypic brain slice culture (BSC) models using long-term optical pulse labeling methodology. Our studies reveal that tau inclusions typically form in 12-96 h in tauopathy BSC models. Unexpectedly, we demonstrate appreciable turnover of tau within inclusions with an average half-life of ~ 1 week when inclusions are newly formed. When BSCs with inclusions are aged in culture for extended periods, tau inclusions continue to turnover, but their half-lives increase to ~ 2 weeks and ~ 3 weeks after 1 and 2 months in culture, respectively. Individual tau inclusions can be long-lived structures that can persist for months in these BSC models and for even longer in the human brain. However, our data indicate that tau inclusions, are not 'tombstones', but dynamic structures with appreciable turnover. Understanding the cellular processes mediating this inclusion turnover may lead to new therapeutic strategies that could reverse pathological tau inclusion formation.
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