ArticleJCI insight2022
Astrocytic 4R tau expression drives astrocyte reactivity and dysfunction.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 38 citations in OpenAlex.
- Engineered Alzheimer Organoids Validate the Link Between Intracellular and Soluble p-Tau Biomarkers and Highlight the Contribution of Astrocytic Tau.Neuroscience bulletin · 2026Article
- Divergent recovery trajectories after mild traumatic brain injury are characterized by distinct acute profiles of neurofilament light, 4R-tau, and white matter diffusivity.Journal of neurology · 2026Article
- Tau pathology in epilepsy: emerging mechanisms and translational opportunities.Brain : a journal of neurology · 2026Review
- Patient-derived forebrain cortical organoids reveal biphasic tau-MAP6-microtubule axis dysfunction in tauopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Tau conformation, distribution and PET imaging correlations in progressive supranuclear palsy.Translational neurodegeneration · 2026Review
- Cell autonomous microglia defects in a stem cell model of frontotemporal dementia tau.Molecular psychiatry · 2025Article
- Understanding Tau pathology: Insights from animal models.Zoological research · 2025Review
- Neurotoxic amyloid β-peptide and tau produce cytokine-like effects on PMCA in glioblastoma cell lines, enhancing its activity and isoforms expression.FEBS open bio · 2025Article
- Article
- Diverse influences on tau aggregation and implications for disease progression.Genes & development · 2025Review
- Tau depletion diminishes vascular amyloid-related deficits in a mouse model of cerebral amyloid angiopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Tau Pathology Drives Disease-Associated Astrocyte Reactivity in Salt-Induced Neurodegeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Upregulated astrocyte HDAC7 induces Alzheimer-like tau pathologies via deacetylating transcription factor-EB and inhibiting lysosome biogenesis.Molecular neurodegeneration · 2025Article
- DYRK1A in the physiology and pathology of the neuron-astrocyte axis.Frontiers in neuroscience · 2025Review
- Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.Cell reports · 2024Article
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.Nature neuroscience · 2024Article
- Diverse signaling mechanisms and heterogeneity of astrocyte reactivity in Alzheimer's disease.Journal of neurochemistry · 2024Review
- Astrocyte tau deposition in progressive supranuclear palsy is associated with dysregulation of MAPT transcription.Acta neuropathologica communications · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
The protein tau and its isoforms are associated with several neurodegenerative diseases, many of which are characterized by greater deposition of the 4-repeat (4R) tau isoform; however, the role of 4R tau in disease pathogenesis remains unclear. We created antisense oligonucleotides (ASOs) that alter the ratio of 3R to 4R tau to investigate the role of specific tau isoforms in disease. Preferential expression of 4R tau in human tau-expressing (hTau-expressing) mice was previously shown to increase seizure severity and phosphorylated tau deposition without neuronal or synaptic loss. In this study, we observed strong colocalization of 4R tau within reactive astrocytes and increased expression of pan-reactive and neurotoxic genes following 3R to 4R tau splicing ASO treatment in hTau mice. Increasing 4R tau levels in primary astrocytes provoked a similar response, including a neurotoxic genetic profile and diminished homeostatic function, which was replicated in human induced pluripotent stem cell-derived (iPSC-derived) astrocytes harboring a mutation that exhibits greater 4R tau. Healthy neurons cultured with 4R tau-expressing human iPSC-derived astrocytes exhibited a higher firing frequency and hypersynchrony, which could be prevented by lowering tau expression. These findings support a potentially novel pathway by which astrocytic 4R tau mediates reactivity and dysfunction and suggest that astrocyte-targeted therapeutics against 4R tau may mitigate neurodegenerative disease progression.
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Registered trials
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.