ArticleScience translational medicine2022
Distinct populations of highly potent TAU seed conformers in rapidly progressing Alzheimer's disease.
Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed.
- α-Synuclein strain homogeneity in multiple system atrophy subtypes.Brain pathology (Zurich, Switzerland) · 2026Article
- Evidence for different seeding activities of misfolded tau in classical and rapidly progressive Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2026Article
- Expression of progerin enhances disease-related endpoints in a tau seeding reporter cell system.GeroScience · 2026Article
- Reduced plasma TIA-1: bridging established pathology and novel biomarker potential.Alzheimer's research & therapy · 2026Article
- A distinct tau oligomer strain defines the molecular and proteomic landscape of rapidly progressive Alzheimer's disease.Acta neuropathologica · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Disulfide engineering reveals unexpected pro- and anti-aggregation conformers of human α-synuclein.bioRxiv : the preprint server for biology · 2026Article
- Morphological and Hyperphosphorylation Transitions of Nanoscale Tau Aggregates in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Seed-competent tau oligomers' activity correlates with the rate of progression in sporadic Alzheimer's disease patients.Journal of Alzheimer's disease : JAD · 2026Article
- 4R-tau seeding activity reveals molecular subtypes in progressive supranuclear palsy.Nature communications · 2025Article
- Prions and protein aggregates as pathogens, self-propagating structures, biomarkers, and therapeutic targets.Microbiology and molecular biology reviews : MMBR · 2025Review
- APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 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
- Article
- Tau-seed interactome analysis reveals distinct functional signatures in Alzheimer's disease across model systems.bioRxiv : the preprint server for biology · 2025Article
- Structural exposure of different microtubule binding domains determines the propagation and toxicity of pathogenic tau conformers in Alzheimer's disease.PLoS pathogens · 2025Article
- Protein co-aggregates of dense core amyloid plaques and CSF differ in rapidly progressive Alzheimer's disease and slower sporadic Alzheimer's disease.Alzheimer's research & therapy · 2025Article
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities.Communications biology · 2025Article
- Exacerbated mitochondrial dynamic abnormalities without evident tau pathology in rapidly progressive Alzheimer's disease.Journal of Alzheimer's disease : JAD · 2024Article
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Authors and funding
12 authors.
Funding
Abstract
Although genetic factors play a main role in determining the risk of developing Alzheimer’s disease (AD), they do not explain extensive spectrum of clinicopathological phenotypes. Deposits of aggregated TAU proteins are one of the main predictors of cognitive decline in AD. We investigated the hypothesis that variabilities in AD progression could be due to diverse structural assemblies (strains) of TAU protein. Using sensitive biophysical methods in 40 patients with AD and markedly different disease durations, we identified populations of distinct TAU particles that differed in size, structural organization, and replication rate in vitro and in cell assay. The rapidly replicating, distinctly misfolded TAU conformers found in rapidly progressive AD were composed of ~80% misfolded four-repeat (4R) TAU and ~20% of misfolded 3R TAU isoform with the same conformational signatures. These biophysical observations suggest that distinctly misfolded population of 4R TAU conformers drive the rapid decline in AD and imply that effective therapeutic strategies might need to consider not a singular species but a cloud of differently misfolded TAU conformers.
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