ArticleScience advances2022
Alzheimer's disease: Ablating single master site abolishes tau hyperphosphorylation.
Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
64 citing papers in PubMed.
- p75 neurotrophin receptor modulation in mild to moderate Alzheimer disease: a randomized, placebo-controlled phase 2a trial.Nature medicine · 2024Trial
- Suvorexant Acutely Decreases Tau Phosphorylation and Aβ in the Human CNS.Annals of neurology · 2023Trial
- Synaptic proteomics identifies cathepsin B as a regulator of synapse remodelling during learning.bioRxiv : the preprint server for biology · 2026Article
- Large-scale single-molecule analysis of tau proteoforms.Nature methods · 2026Article
- Aberrant histone acetylation and dysregulated synaptic plasticity in cognitive impairment induced by a high-methionine diet.Neural regeneration research · 2026Article
- Review
- Engineering a Novel Bacterial Encapsulin for Programmable Surface Functionalization: From Single-Target to Mosaic Nanovaccines.bioRxiv : the preprint server for biology · 2026Article
- Aberrant tau accumulation caused by MAPT mutations induces early pathological changes in axonal transport that are rescued by p38α inhibition.Nature neuroscience · 2026Article
- Tau T205 phosphorylation modulates engram cell recruitment and remote memory in mice.Nature communications · 2026Article
- Suppression of Tau Phosphorylation Induces Neurotoxicity, Causing Developmental Defects and Degeneration inCells · 2026Article
- Neuroprotective Mechanisms of Ficus deltoidea in an Alzheimer's Disease-Like Rat Model: Targeting Tau Hyperphosphorylation Through Glycogen Synthase Kinase-3 Beta and Protein Phosphatase 2A Regulation.Neurochemical research · 2026Article
- Article
- Procoagulant Extracellular Vesicles Increase Neuronal Tau expression, Metabolism and Processing Through Tissue Factor and Protease Activated Receptor 2.Cellular and molecular neurobiology · 2026Article
- CSF peptidomics reveals an IGF2-derived peptide as a candidate biomarker for neurosyphilis diagnosis.Frontiers in microbiology · 2026Article
- Pretangle tau pathology accrual in the default mode network during the progression of Alzheimer's disease.Molecular neurodegeneration advances · 2026Article
- Therapeutic potential of vagus nerve stimulation in neurodegenerative diseases: research progress and mechanisms.Frontiers in immunology · 2026Review
- O- and N-Phosphoproteomic Analysis Using Online Alkaline-pH Reversed-Phase Nanoelectrospray-Tandem Mass Spectrometry.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Post-translational modifications as a regulatory code for tau function in health and disease.Frontiers in dementia · 2026Review
- Morphological and Hyperphosphorylation Transitions of Nanoscale Tau Aggregates in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Modeling Alzheimer's disease with brain organoids: mechanisms, applications, and future directions.Frontiers in cell and developmental biology · 2026Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperphosphorylation of the neuronal tau protein is a hallmark of neurodegenerative tauopathies such as Alzheimer's disease. A central unanswered question is why tau becomes progressively hyperphosphorylated. Here, we show that tau phosphorylation is governed by interdependence- a mechanistic link between initial site-specific and subsequent multi-site phosphorylation. Systematic assessment of site interdependence identified distinct residues (threonine-50, threonine-69, and threonine-181) as master sites that determine propagation of phosphorylation at multiple epitopes. CRISPR point mutation and expression of human tau in Alzheimer's mice showed that site interdependence governs physiologic and amyloid-associated multi-site phosphorylation and cognitive deficits, respectively. Combined targeting of master sites and p38α, the most central tau kinase linked to interdependence, synergistically ablated hyperphosphorylation. In summary, our work delineates how complex tau phosphorylation arises to inform therapeutic and biomarker design for tauopathies.
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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.