ArticleActa neuropathologica communications2019
Therapeutic antibody targeting microtubule-binding domain prevents neuronal internalization of extracellular tau via masking neuron surface proteoglycans.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- Post hoc analysis of ADAMANT, a phase 2 clinical trial of active tau immunotherapy with AADvac1 in patients with Alzheimer's disease, positive for plasma p-tau217.Alzheimer's research & therapy · 2024Trial
- ADAMANT: a placebo-controlled randomized phase 2 study of AADvac1, an active immunotherapy against pathological tau in Alzheimer's disease.Nature aging · 2021Trial
- Ganglioside sialylation modulates tau internalization and pathology spread.Molecular psychiatry · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Heparin treatment is associated with a delayed diagnosis of Alzheimer's dementia in electronic health records from two large United States health systems.Molecular psychiatry · 2025Article
- Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- dGAE(297-391) Tau Fragment Promotes Formation of Chronic Traumatic Encephalopathy-Like Tau Filaments.Angewandte Chemie (International ed. in English) · 2024Article
- Targeting Endogenous Tau in Seeded Tauopathy Models Inhibits Tau Spread.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Pathological tau signatures and nuclear alterations in neurons, astrocytes and microglia in Alzheimer's disease, progressive supranuclear palsy, and dementia with Lewy bodies.Brain pathology (Zurich, Switzerland) · 2023Article
- Microtube Array Membrane Encapsulated Cell Therapy: A Novel Platform Technology Solution for Treatment of Alzheimer's Disease.International journal of molecular sciences · 2022Article
- The Role of Extracellular Matrix Components in the Spreading of Pathological Protein Aggregates.Frontiers in cellular neuroscience · 2022Review
- A sporadic Alzheimer's blood-brain barrier model for developing ultrasound-mediated delivery of Aducanumab and anti-Tau antibodies.Theranostics · 2022Article
- The role of pathological tau in synaptic dysfunction in Alzheimer's diseases.Translational neurodegeneration · 2021Review
- Tau Post-Translational Modifications: Potentiators of Selective Vulnerability in Sporadic Alzheimer's Disease.Biology · 2021Review
- Therapeutic Ultrasound as a Treatment Modality for Physiological and Pathological Ageing Including Alzheimer's Disease.Pharmaceutics · 2021Review
- Heparan sulfate proteoglycans as possible diagnostic molecular tools with therapeutic potential in Alzheimer´s disease.Neural regeneration research · 2021Article
- CSF tau microtubule binding region identifies tau tangle and clinical stages of Alzheimer's disease.Brain : a journal of neurology · 2021Article
- The Sulfation Code of Tauopathies: Heparan Sulfate Proteoglycans in the Prion Like Spread of Tau Pathology.Frontiers in molecular biosciences · 2021Review
- Fate and propagation of endogenously formed Tau aggregates in neuronal cells.EMBO molecular medicine · 2020Article
- Conformation-selective tau monoclonal antibodies inhibit tau pathology in primary neurons and a mouse model of Alzheimer's disease.Molecular neurodegeneration · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathologically altered tau protein is a common denominator of neurodegenerative disorders including Alzheimer's disease (AD) and other tauopathies. Therefore, promising immunotherapeutic approaches target and eliminate extracellular pathogenic tau species, which are thought to be responsible for seeding and propagation of tau pathology. Tau isoforms in misfolded states can propagate disease pathology in a template-dependent manner, proposed to be mediated by the release and internalization of extracellular tau. Monoclonal antibody DC8E8, binding four highly homologous and independent epitopes in microtubule-binding domain (MTBD) of diseased tau, inhibits tau-tau interaction, discriminates between healthy and pathologically truncated tau and reduces tau pathology in animal model in vivo. Here, we show that DC8E8 antibody acts via extracellular mechanism and does not influence viability and physiological functions of neurons. Importantly, in vitro functional assays showed that DC8E8 recognises pathogenic tau proteins of different size and origin, and potently blocks their entry into neurons. Next, we examined the mechanisms by which mouse antibody DC8E8 and its humanized version AX004 effectively block the neuronal internalization of extracellular AD tau species. We determined a novel mode of action of a therapeutic candidate antibody, which potently inhibits neuronal internalization of AD tau species by masking of epitopes present in MTBD important for interaction with neuron surface Heparan Sulfate Proteoglycans (HSPGs). We show that interference of tau-heparane sulfate interaction with DC8E8 antibody via steric hindrance represents an efficient and important therapeutic approach halting tau propagation.
Indexed as
Identifiers
What OpenQuestion holds
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.