ArticleScientific reports2016
Structure of Crenezumab Complex with Aβ Shows Loss of β-Hairpin.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
What it found
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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.
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
69 citing papers in PubMed.
- 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
- Passive amyloid-β immunotherapy in Alzheimer's disease: a multicellular clearance system beyond plaque removal.Molecular neurodegeneration · 2026Review
- Could the cognitive benefits of amyloid-beta clearance grow in time for Alzheimer's disease?Translational psychiatry · 2026Review
- A Narrative Review of Amyloid-β Monoclonal Antibodies for Alzheimer Disease: How Amyloid Species Engagement May Affect Clinical Outcomes.The neurologist · 2026Review
- Targeting amyloid-β pathology by chimeric antigen receptor astrocyte (CAR-A) therapy.Science (New York, N.Y.) · 2026Article
- Article
- Rationally Designed Pentapeptide Analogs of Aβ19-23 Fragment as Potent Inhibitors of Aβ42 Aggregation.Molecules (Basel, Switzerland) · 2025Article
- Amyloid-β-regulated gene circuits for programmable Alzheimer's disease therapy.bioRxiv : the preprint server for biology · 2025Article
- Second-generation anti-amyloid monoclonal antibodies for Alzheimer's disease: current landscape and future perspectives.Translational neurodegeneration · 2025Review
- Amyloid-β Clearance with Monoclonal Antibodies: Transforming Alzheimer's Treatment.Current protein & peptide science · 2025Review
- Conventional and Emerging Drug Targeting Sites in Alzheimer's Disease and the Role of Translational Informatics in its Diagnosis and Management.Current neuropharmacology · 2025Review
- Replacement of a single residue in an antibody abolishes cognate antigen binding, as predicted by theoretical methods.Computational and structural biotechnology journal · 2025Article
- Passive Anti-amyloid Beta Monoclonal Antibodies: Lessons Learned over Past 20 Years.Neurology and therapy · 2024Review
- Alzheimer's Disease Immunotherapy and Mimetic Peptide Design for Drug Development: Mutation Screening, Molecular Dynamics, and a Quantum Biochemistry Approach Focusing on Aducanumab::Aβ2-7 Binding Affinity.ACS chemical neuroscience · 2024Article
- Limitations and potential strategies of immune checkpoint blockade in age-related neurodegenerative disorders.The journal of physiological sciences : JPS · 2024Review
- Humanin variant P3S is associated with longevity in APOE4 carriers and resists APOE4-induced brain pathology.Aging cell · 2024Article
9 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
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulation of amyloid-β (Aβ) peptides and amyloid plaque deposition in brain is postulated as a cause of Alzheimer's disease (AD). The precise pathological species of Aβ remains elusive although evidence suggests soluble oligomers may be primarily responsible for neurotoxicity. Crenezumab is a humanized anti-Aβ monoclonal IgG4 that binds multiple forms of Aβ, with higher affinity for aggregated forms, and that blocks Aβ aggregation, and promotes disaggregation. To understand the structural basis for this binding profile and activity, we determined the crystal structure of crenezumab in complex with Aβ. The structure reveals a sequential epitope and conformational requirements for epitope recognition, which include a subtle but critical element that is likely the basis for crenezumab's versatile binding profile. We find interactions consistent with high affinity for multiple forms of Aβ, particularly oligomers. Of note, crenezumab also sequesters the hydrophobic core of Aβ and breaks an essential salt-bridge characteristic of the β-hairpin conformation, eliminating features characteristic of the basic organization in Aβ oligomers and fibrils, and explains crenezumab's inhibition of aggregation and promotion of disaggregation. These insights highlight crenezumab's unique mechanism of action, particularly regarding Aβ oligomers, and provide a strong rationale for the evaluation of crenezumab as a potential AD therapy.
Identifiers
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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.