Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
An effector-reduced anti-β-amyloid (Aβ) antibody with unique aβ binding properties promotes neuroprotection and glial engulfment of Aβ.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 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
157 citing papers in PubMed, 306 citations in OpenAlex.
- Pharmacokinetics and pharmacodynamic effect of crenezumab on plasma and cerebrospinal fluid beta-amyloid in patients with mild-to-moderate Alzheimer's disease.Alzheimer's research & therapy · 2020Trial
- Safety, Tolerability, and Pharmacokinetics of Crenezumab in Patients with Mild-to-Moderate Alzheimer's Disease Treated with Escalating Doses for up to 133 Weeks.Journal of Alzheimer's disease : JAD · 2020Trial
- Target engagement in an alzheimer trial: Crenezumab lowers amyloid β oligomers in cerebrospinal fluid.Annals of neurology · 2019Trial
- Amyloid positron emission tomography and cerebrospinal fluid results from a crenezumab anti-amyloid-beta antibody double-blind, placebo-controlled, randomized phase II study in mild-to-moderate Alzheimer's disease (BLAZE).Alzheimer's research & therapy · 2018Trial
- ABBY: A phase 2 randomized trial of crenezumab in mild to moderate Alzheimer disease.Neurology · 2018Trial
- Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy.Science (New York, N.Y.) · 2026Article
- Translating Alzheimer's Disease Mechanisms into Therapeutic Opportunities.Biomolecules · 2025Review
- Review
- Amyloid-β-regulated gene circuits for programmable Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2025Article
- ABTrans: A Transformer-based Model for Predicting Interaction between Anti-Aβ Antibodies and Peptides.Interdisciplinary sciences, computational life sciences · 2025Article
- Review
- Drug delivery strategies with lipid-based nanoparticles for Alzheimer's disease treatment.Journal of nanobiotechnology · 2025Review
- From Genetics to Neuroinflammation: The Impact of ApoE4 on Microglial Function in Alzheimer's Disease.Cells · 2025Review
- Second-generation anti-amyloid monoclonal antibodies for Alzheimer's disease: current landscape and future perspectives.Translational neurodegeneration · 2025Review
- Evolution of Alzheimer's Disease Therapeutics: From Conventional Drugs to Medicinal Plants, Immunotherapy, Microbiotherapy and Nanotherapy.Pharmaceutics · 2025Review
- Amyloid-β Clearance with Monoclonal Antibodies: Transforming Alzheimer's Treatment.Current protein & peptide science · 2025Review
- Passive Anti-amyloid Beta Monoclonal Antibodies: Lessons Learned over Past 20 Years.Neurology and therapy · 2024Review
- Demystifying the Role of Neuroinflammatory Mediators as Biomarkers for Diagnosis, Prognosis, and Treatment of Alzheimer's Disease: A Review.ACS pharmacology & translational science · 2024Review
- Application of mesenchymal stem cells for neurodegenerative diseases therapy discovery.Regenerative therapy · 2024Review
- Article
97 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Passive immunization against β-amyloid (Aβ) has become an increasingly desirable strategy as a therapeutic treatment for Alzheimer's disease (AD). However, traditional passive immunization approaches carry the risk of Fcγ receptor-mediated overactivation of microglial cells, which may contribute to an inappropriate proinflammatory response leading to vasogenic edema and cerebral microhemorrhage. Here, we describe the generation of a humanized anti-Aβ monoclonal antibody of an IgG4 isotype, known as MABT5102A (MABT). An IgG4 subclass was selected to reduce the risk of Fcγ receptor-mediated overactivation of microglia. MABT bound with high affinity to multiple forms of Aβ, protected against Aβ1-42 oligomer-induced cytotoxicity, and increased uptake of neurotoxic Aβ oligomers by microglia. Furthermore, MABT-mediated amyloid plaque removal was demonstrated using in vivo live imaging in hAPP((V717I))/PS1 transgenic mice. When compared with a human IgG1 wild-type subclass, containing the same antigen-binding variable domains and with equal binding to Aβ, MABT showed reduced activation of stress-activated p38MAPK (p38 mitogen-activated protein kinase) in microglia and induced less release of the proinflammatory cytokine TNFα. We propose that a humanized IgG4 anti-Aβ antibody that takes advantage of a unique Aβ binding profile, while also possessing reduced effector function, may provide a safer therapeutic alternative for passive immunotherapy for AD. Data from a phase I clinical trial testing MABT is consistent with this hypothesis, showing no signs of vasogenic edema, even in ApoE4 carriers.
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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.