ArticleAlzheimer's research & therapy2019
Amyloid β-protein oligomers promote the uptake of tau fibril seeds potentiating intracellular tau aggregation.
Article in Alzheimer's research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Diagnosis Test Meta-Analysis for Apolipoprotein E in Alzheimer's Disease.Disease markers · 2020Pooled it
- Mediterranean and Western diet effects on Alzheimer's disease biomarkers, cerebral perfusion, and cognition in mid-life: A randomized trial.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Trial
- Neuroprotective effects of SRS11-92 against oxidative stress-induced senescence via Nrf2/HO-1/NF-κB in Alzheimer's disease models.Inflammopharmacology · 2026Article
- Rigor & Reproducibility: pH Adjustments of Papain with L-Cysteine Dissociation Solutions and Cell Media Using Phenol Red Spectrophotometry.Biosensors · 2025Article
- Fluidic Programmable Gravi-maze Array for High Throughput Multiorgan Drug Testing.bioRxiv : the preprint server for biology · 2025Article
- Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.Cell stem cell · 2025Article
- Experimental methods for studying amyloid cross-interactions.Protein science : a publication of the Protein Society · 2025Review
- Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease.Archiv der Pharmazie · 2025Review
- FGFR3 drives Aβ-induced tau uptake.Experimental & molecular medicine · 2024Article
- Neuropathogenesis-on-chips for neurodegenerative diseases.Nature communications · 2024Review
- Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases.Molecular neurodegeneration · 2024Review
- Comprehensive Insights into Pathophysiology of Alzheimer's Disease: Herbal Approaches for Mitigating Neurodegeneration.Current Alzheimer research · 2024Review
- Re-Arranging the Puzzle between the Amyloid-Beta and Tau Pathology: An APP-Centric Approach.International journal of molecular sciences · 2023Review
- Review
- Differential Binding and Conformational Dynamics of Tau Microtubule-Binding Repeats with a Preformed Amyloid-β Fibril Seed.ACS chemical neuroscience · 2023Article
- Anti-Neuroinflammatory Potential of Natural Products in the Treatment of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2023Review
- Using FRET-Based Biosensor Cells to Study the Seeding Activity of Tau and α-Synuclein.Methods in molecular biology (Clifton, N.J.) · 2023Article
- The Interplay between GSK3β and Tau Ser262 Phosphorylation during the Progression of Tau Pathology.International journal of molecular sciences · 2022Article
- LC-MS/MS Insight into Vitamin C Restoration to Metabolic Disorder Evoked by Amyloid β inMetabolites · 2022Article
- Aβ/tau oligomer interplay at human synapses supports shifting therapeutic targets for Alzheimer's disease.Cellular and molecular life sciences : CMLS · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors.
Funding
Abstract
backgroundRepeated failure of drug candidates targeting Alzheimer's disease (AD) in clinical trials likely stems from a lack of understanding of the molecular mechanisms underlying AD pathogenesis. Recent research has highlighted synergistic interactions between aggregated amyloid-β (Aβ) and tau proteins in AD, but the molecular details of how these interactions drive AD pathology remain elusive and speculative.
methodsHere, we test the hypothesis that Aβ potentiates intracellular tau aggregation, and show that oligomeric Aβ specifically exacerbates proteopathic seeding by tau. Using tau-biosensor cells, we show that treatment with sub-toxic concentrations of Aβ oligomers, but not monomers or fibrils, "primes" cells, making them more susceptible to tau seeding. The treatment with Aβ oligomers enhances intracellular tau aggregation in a dose-dependent manner when the cells are seeded with either recombinant or brain-derived tau fibrils, whereas little or no aggregation is observed in the absence of Aβ-oligomer priming.
resultsPriming by Aβ oligomers appears to be specific to tau, as α-synuclein seeding is unaffected by this treatment. Aβ oligomer-enhanced tau seeding also occurs in primary mouse neurons and human neuroblastoma cells. Using fluorescently labeled tau seeds, we find that treatment with Aβ oligomers significantly enhances the cellular uptake of tau seeds, whereas a known tau-uptake inhibitor blocks the effect of Aβ on tau uptake.
conclusionThe ability of Aβ to promote tau seeding suggests a specific and plausible mechanism by which extracellular Aβ initiates a deleterious cascade that is unique to AD. These data suggest that the Aβ-mediated potentiation of tau uptake into cells should also be taken into account when designing Aβ-targeted therapeutics.
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