ArticleCell death & disease2020
Internalization mechanisms of brain-derived tau oligomers from patients with Alzheimer's disease, progressive supranuclear palsy and dementia with Lewy bodies.
Article in Cell death & disease, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 104 citations in OpenAlex.
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Limited Detectability of Network Functional Alterations in a Tauopathy Model Using Mouse Primary Cortical Cultures.Biomedicines · 2026Article
- Connexin 50 mediates disease-relevant alpha-synuclein oligomer propagation and neuroinflammation in neurodegenerative disease.iScience · 2026Article
- Nuclear dysfunction in aging and neurodegeneration.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Mitochondrial NADK2-dependent NADPH controls tau oligomer uptake in human neurons.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Selective reduction of KCNA4 in vulnerable glutamatergic-serotonin neurons of the dorsal raphe nucleus in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Selective vulnerability of human synapses to soluble tau oligomers.Journal of Alzheimer's disease : JAD · 2026Article
- Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.Molecular neurodegeneration · 2026Article
- P2X7 receptor-dependent microglia-astrocyte coupling in Alzheimer's disease: from eATP sensing to synaptic and proteostatic failure.Frontiers in aging neuroscience · 2026Review
- APOE isoform-associated tau oligomer polymorphs differ in synaptotoxicity and seeding activity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Entwined processes in Alzheimer's disease: Brain cellular senescence and Alzheimer's disease pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Making tau amyloid models in vitro: a crucial and underestimated challenge.FEBS letters · 2025Review
- Cryo-EM structural analyses reveal diverse porous structures in brain-derived tau oligomers.Biochemical and biophysical research communications · 2025Article
- Tau Oligomers in Alzheimer's Disease: Modulation Effect of Osmolytes on Amplified Brain-Derived Tau Oligomers.ACS chemical neuroscience · 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
- Reciprocal Interactions Between Periodontal Disease and Alzheimer's Disease: Implications for Mutual Triggering, Exacerbation, and Treatment Interventions-A Comprehensive Review of the Literature.Neurology international · 2025Review
- Hippocampal Neural Stem Cell Exosomes Promote Brain Resilience against the Impact of Tau Oligomers.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Pathogenic oligomeric Tau alters neuronal RNA processes through the formation of nuclear heteromeric amyloids with RNA-binding protein Musashi1.Progress in neurobiology · 2025Article
- Retinal ganglion cell vulnerability to pathogenic tau in Alzheimer's disease.Acta neuropathologica communications · 2025Article
- Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities.Communications biology · 2025Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Tau aggregates propagate in brain cells and transmit to neighboring cells as well as anatomically connected brain regions by prion-like mechanisms. Soluble tau aggregates (tau oligomers) are the most toxic species that initiate neurodegeneration in tauopathies, such as Alzheimer's disease (AD), progressive supranuclear palsy (PSP), and dementia with Lewy bodies (DLB). Exogenous tau aggregates have been shown to be internalized by brain cells; however, the precise cellular and molecular mechanisms that underlie the internalization of tau oligomers (TauO) remain elusive. Using brain-derived tau oligomers (BDTOs) from AD, PSP, and DLB patients, we investigated neuronal internalization mechanisms of BDTOs, including the heparan sulfate proteoglycan (HSPG)-mediated pathway, clathrin-mediated pathway, and caveolae-mediated pathway. Here, we demonstrated that the HSPG-mediated pathway regulates internalization of BDTOs from AD and DLB, while HSPG-mediated and other alternative pathways are involved in the internalization of PSP-derived tau oligomers. HSPG antagonism significantly reduced the internalization of TauO, prevented tau translocation to the endosomal-lysosomal system, and decreased levels of hyperphosphorylated tau in neurons, the well-known contributor for neurofibrillary tangles (NFT) accumulation, degeneration of neurons, and cognitive decline. Furthermore, siRNA-mediated silencing of heparan sulfate (HS)-synthesizing enzyme, exostosin-2, leads to decreased internalization of BDTOs, prevented tau-induced autophagy-lysosomal pathway impairment, and decreased hyperphosphorylated tau levels. Collectively, these findings suggest that HSPG-mediated endocytosis and exostsin-2 are involved in neuronal internalization of TauO and subsequent tau-dependent neuropathology in AD and DLB.
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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.