ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Neutralization of soluble, synaptotoxic amyloid β species by antibodies is epitope specific.
Article 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 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Bapineuzumab for mild to moderate Alzheimer's disease: a meta-analysis of randomized controlled trials.BMC neurology · 2017Pooled it
- Two phase 3 trials of bapineuzumab in mild-to-moderate Alzheimer's disease.The New England journal of medicine · 2014Trial
- Non-Coding DNA-Derived Mimotopes of Aβ₄₂ as Novel Candidates for Alzheimer's Peptide Vaccine Design.International journal of medical sciences · 2026Article
- Amyloid beta 42 alters cardiac metabolism and impairs cardiac function in male mice with obesity.Nature communications · 2024Article
- Bioactive human Alzheimer brain soluble Aβ: pathophysiology and therapeutic opportunities.Molecular psychiatry · 2022Review
- Structural biology of cell surface receptors implicated in Alzheimer's disease.Biophysical reviews · 2022Review
- Enzyme-digestedNeural regeneration research · 2020Article
- Immunotherapies for Aging-Related Neurodegenerative Diseases-Emerging Perspectives and New Targets.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2020Review
- Chronic Presence of Oligomeric Aβ Differentially Modulates Spine Parameters in the Hippocampus and Cortex of Mice With Low APP Transgene Expression.Frontiers in synaptic neuroscience · 2020Article
- Article
- ATM phosphorylation of the actin-binding protein drebrin controls oxidation stress-resistance in mammalian neurons and C. elegans.Nature communications · 2019Article
- Active full-length DNA AβAlzheimer's research & therapy · 2018Article
- Decoding the synaptic dysfunction of bioactive human AD brain soluble Aβ to inspire novel therapeutic avenues for Alzheimer's disease.Acta neuropathologica communications · 2018Article
- Emergence of Alternative Structures in Amyloid Beta 1-42 Monomeric Landscape by N-terminal Hexapeptide Amyloid Inhibitors.Scientific reports · 2017Article
- Amino-Terminal β-Amyloid Antibody Blocks β-Amyloid-Mediated Inhibition of the High-Affinity Choline Transporter CHT.Frontiers in molecular neuroscience · 2017Article
- Reduced Efficacy of Anti-Aβ Immunotherapy in a Mouse Model of Amyloid Deposition and Vascular Cognitive Impairment Comorbidity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Decreased amyloid-β and increased neuronal hyperactivity by immunotherapy in Alzheimer's models.Nature neuroscience · 2015Article
- Anti-Aβ antibodies incapable of reducing cerebral Aβ oligomers fail to attenuate spatial reference memory deficits in J20 mice.Neurobiology of disease · 2015Article
- Alzheimer's protective A2T mutation changes the conformational landscape of the Aβ₁₋₄₂ monomer differently than does the A2V mutation.Biophysical journal · 2015Article
- Cerebrospinal fluid biomarkers in trials for Alzheimer and Parkinson diseases.Nature reviews. Neurology · 2015Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several anti-amyloid β (Aβ) antibodies are under evaluation for the treatment of Alzheimer's disease (AD). Clinical studies using the N-terminal-directed anti-Aβ antibody bapineuzumab have demonstrated reduced brain PET-Pittsburg-B signals, suggesting the reduction of Aβ plaques, and reduced levels of total and phosphorylated tau protein in the CSF of treated AD patients. Preclinical studies using 3D6 (the murine form of bapineuzumab) have demonstrated resolution of Aβ plaque and vascular burdens, neuritic dystrophy, and preservation of synaptic density in the transgenic APP mouse models. In contrast, few studies have evaluated the direct interaction of this antibody with synaptotoxic soluble Aβ species. In the current report, we demonstrated that 3D6 binds to soluble, synaptotoxic assemblies of Aβ(1-42) and prevents multiple downstream functional consequences in rat hippocampal neurons including changes in glutamate AMPA receptor trafficking, AD-type tau phosphorylation, and loss of dendritic spines. In vivo, we further demonstrated that 3D6 prevents synaptic loss and acutely reverses the behavioral deficit in the contextual fear conditioning task in transgenic mouse models of AD, two endpoints thought to be linked to synaptotoxic soluble Aβ moieties. Importantly C-terminal anti-Aβ antibodies were ineffective on these endpoints. These results, taken with prior studies, suggest that N-terminal anti-Aβ antibodies effectively interact with both soluble and insoluble forms of Aβ and therefore appear particularly well suited for testing the Aβ hypothesis of AD.
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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.