ArticleAlzheimer's research & therapy2020
Effector function of anti-pyroglutamate-3 Aβ antibodies affects cognitive benefit, glial activation and amyloid clearance in Alzheimer's-like mice.
Article in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Safety and efficacy of crenezumab in cognitively unimpaired carriers of the PSEN1The Lancet. Neurology · 2026Trial
- Immunohistochemical evaluation of a trial of gantenerumab or solanezumab in dominantly inherited Alzheimer disease.Acta neuropathologica · 2025Trial
- Research progress on the role of CD14 in osteoarthritis.Frontiers in immunology · 2026Review
- Review
- Post-Translational Modifications Distinguish Amyloid-β Isoforms in Cerebral Amyloid Angiopathy and Alzheimer's Disease.Journal of neurochemistry · 2025Article
- Early intervention anti-Aβ immunotherapy attenuates microglial activation without inducing exhaustion at residual plaques.Molecular neurodegeneration · 2025Article
- An Overview of Glutaminyl Cyclase as a Promising Drug Target for Alzheimer's Disease.Biomedicines · 2025Article
- Anti-pyroglutamate-3 Aβ immunotherapy engages microglia and inhibits amyloid accumulation in transgenic mouse models of Aβ amyloidosis.Acta neuropathologica · 2025Article
- Effect of Adipokinetic Hormone on Learning-Memory in a Scopolamine-Induced Alzheimer's Model in Mice.Protein and peptide letters · 2025Article
- Visualising the Knowledge Structure of Microglia in Alzheimer's Disease: A CiteSpace Analysis.Journal of multidisciplinary healthcare · 2025Article
- Identification of isoAsp7-Aβ as a major Aβ variant in Alzheimer's disease, dementia with Lewy bodies and vascular dementia.Acta neuropathologica · 2024Article
- Amyloid-β peptide signature associated with cerebral amyloid angiopathy in familial Alzheimer's disease with APPdup and Down syndrome.Acta neuropathologica · 2024Article
- Engineered Antibodies to Improve Efficacy against Neurodegenerative Disorders.International journal of molecular sciences · 2024Review
- Synthesis and Evaluation of a Novel PET Radioligand for Imaging Glutaminyl Cyclase Activity as a Biomarker for Detecting Alzheimer's Disease.ACS sensors · 2024Article
- Amyloid-beta antibody binding to cerebral amyloid angiopathy fibrils and risk for amyloid-related imaging abnormalities.Scientific reports · 2024Article
- Taming microglia: the promise of engineered microglia in treating neurological diseases.Journal of neuroinflammation · 2024Review
- A case for seeking sex-specific treatments in Alzheimer's disease.Frontiers in aging neuroscience · 2024Review
- A combined physiologically-based pharmacokinetic and quantitative systems pharmacology model for modeling amyloid aggregation in Alzheimer's disease.CPT: pharmacometrics & systems pharmacology · 2023Article
- Enhanced delivery of a low dose of aducanumab via FUS in 5×FAD mice, an AD model.Translational neurodegeneration · 2022Article
- Review
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundPyroglutamate-3 Aβ (pGlu-3 Aβ) is an N-terminally truncated and post-translationally modified Aβ species found in Alzheimer's disease (AD) brain. Its increased peptide aggregation propensity and toxicity make it an attractive emerging treatment strategy for AD. We address the question of how the effector function of an anti-pGlu-3 Aβ antibody influences the efficacy of immunotherapy in mouse models with AD-like pathology.
methodsWe compared two different immunoglobulin (Ig) isotypes of the same murine anti-pGlu-3 Aβ mAb (07/1 IgG1 and 07/2a IgG2a) and a general N-terminal Aβ mAb (3A1 IgG1) for their ability to clear Aβ and protect cognition in a therapeutic passive immunotherapy study in aged, plaque-rich APP
resultsWe demonstrated significant cognitive improvement, better plaque clearance, and more plaque-associated microglia in the absence of microhemorrhage in aged APP
conclusionOur results suggest that attenuation of behavioral deficits and clearance of amyloid is associated with strong effector function of the anti-pGlu-3 Aβ mAb in a therapeutic treatment paradigm. We present evidence that antibody engineering to reduce CDC-mediated complement binding facilitates phagocytosis of plaques without inducing neuroinflammation in vivo. Hence, the results provide implications for tailoring effector function of humanized antibodies for clinical 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.