ArticleActa neuropathologica communications2020
Humanized tau antibodies promote tau uptake by human microglia without any increase of inflammation.
Article in Acta neuropathologica communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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.
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Who cites it
19 citing papers in PubMed, 37 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
- Timing matters: early administration of a high-affinity antibody targeting the tau repeat domain prevents aggregation in a mouse tauopathy model.Alzheimer's research & therapy · 2026Article
- Targeting protein aggregate co-pathologies in neurodegeneration: a viable therapeutic strategy?Molecular neurodegeneration advances · 2026Review
- Clearing truncated tau protein restores neuronal function and prevents microglia activation in tauopathy mice.Cell reports · 2025Article
- Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Article
- Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies.Translational neurodegeneration · 2024Review
- Measuring Antibody-Mediated Tau Fibril Uptake in Microglia by Flow Cytometry.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Tau Immunotherapies for Alzheimer's Disease and Related Tauopathies: Status of Trials and Insights from Preclinical Studies.Journal of Alzheimer's disease : JAD · 2024Review
- Roles in Innate Immunity.Advances in neurobiology · 2024Review
- Tau-targeting therapies for Alzheimer disease: current status and future directions.Nature reviews. Neurology · 2023Review
- The past and present of therapeutic strategy for Alzheimer's diseases: potential for stem cell therapy.Experimental animals · 2023Review
- Astrocytes express aberrant immunoglobulins as putative gatekeeper of astrocytes to neuronal progenitor conversion.Cell death & disease · 2023Article
- Microglia: Friend and foe in tauopathy.Progress in neurobiology · 2022Review
- Targeting tau only extracellularly is likely to be less efficacious than targeting it both intra- and extracellularly.Seminars in cell & developmental biology · 2022Review
- Passive immunization against phosphorylated tau improves features of Huntington's disease pathology.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Delivery of Intravenously Administered Antibodies Targeting Alzheimer's Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis.Pharmaceutics · 2022Review
- Microglial autophagy in Alzheimer's disease and Parkinson's disease.Frontiers in aging neuroscience · 2022Review
- A Levee to the Flood: Pre-injury Neuroinflammation and Immune Stress Influence Traumatic Brain Injury Outcome.Frontiers in aging neuroscience · 2021Review
- Alzheimer's Risk Gene TREM2 Determines Functional Properties of New Type of Human iPSC-Derived Microglia.Frontiers in immunology · 2020Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapies targeting pathological tau have recently emerged as a promising approach for treatment of neurodegenerative disorders. We have previously showed that the mouse antibody DC8E8 discriminates between healthy and pathological tau, reduces tau pathology in murine tauopathy models and inhibits neuronal internalization of AD tau species in vitro.Here we show, that DC8E8 and antibodies elicited against the first-in-man tau vaccine, AADvac1, which is based on the DC8E8 epitope peptide, both promote uptake of pathological tau by mouse primary microglia. IgG1 and IgG4 isotypes of AX004, the humanized versions of DC8E8, accelerate tau uptake by human primary microglia isolated from post-mortem aged and diseased brains. This promoting activity requires the presence of the Fc-domain of the antibodies.The IgG1 isotype of AX004 showed greater ability to promote tau uptake compared to the IgG4 isotype, while none of the antibody-tau complexes provoked increased pro-inflammatory activity of microglia. Our data suggest that IgG1 has better suitability for therapeutic development.
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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.