Trial reportAnnals of neurology2019
Target engagement in an alzheimer trial: Crenezumab lowers amyloid β oligomers in cerebrospinal fluid.
Trial report in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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.
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
51 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
- Multimerization of a rationally designed nanobody for enhanced avidity toward Aβ42 oligomers.Protein science : a publication of the Protein Society · 2026Article
- A manifesto for Alzheimer's disease drug discovery in the era of disease-modifying therapies.Molecular neurodegeneration · 2025Review
- Alzheimer disease: Amyloid peptide controversies and challenges of anti-Aβ immunotherapy.The Journal of pharmacology and experimental therapeutics · 2025Review
- An improved immunoassay detects Aβ oligomers in human biofluids: their CSF levels rise with tau and phosphotau levels.Alzheimer's research & therapy · 2025Article
- Newer Therapeutic Approaches in Treating Alzheimer's Disease: A Comprehensive Review.ACS omega · 2025Review
- Comprehending Alzheimer's Disease: Molecular Mechanisms and Treatment Strategies.Current Alzheimer research · 2025Review
- Review
- Emerging Roles of Adaptive Immune Response in Alzheimer's Disease.Aging and disease · 2024Review
- α-Tocotrienol Protects Neurons by Preventing Tau Hyperphosphorylation via Inhibiting Microtubule Affinity-Regulating Kinase Activation.International journal of molecular sciences · 2024Article
- Ultrasensitive and Multiple Biomarker Discrimination for Alzheimer's Disease via Plasmonic & Microfluidic Sensing Technologies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Novel Therapeutic Strategies in Alzheimer's Disease: Pitfalls and Challenges of Anti-Amyloid Therapies and Beyond.Journal of clinical medicine · 2024Review
- Proteomics revealed an association between ribosome-associated proteins and amyloid beta deposition in Alzheimer's disease.Metabolic brain disease · 2024Article
- EPR Studies of Aβ42 Oligomers Indicate a Parallel In-Register β-Sheet Structure.ACS chemical neuroscience · 2024Article
- Prevention and Treatment Strategies for Alzheimer's Disease: Focusing on Microglia and Astrocytes in Neuroinflammation.Journal of inflammation research · 2024Review
- Amyloid-Directed Antibodies: Past, Present, and Future.Journal of Alzheimer's disease : JAD · 2024Review
- Review
- Investigational treatments for neurodegenerative diseases caused by inheritance of gene mutations: lessons from recent clinical trials.Neural regeneration research · 2023Review
- Antibody-Mediated Clearance of Brain Amyloid-β: Mechanisms of Action, Effects of Natural and Monoclonal Anti-Aβ Antibodies, and Downstream Effects.Journal of Alzheimer's disease reports · 2023Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
objectiveOligomeric forms of amyloid β protein (oAβ) are believed to be principally responsible for neurotoxicity in Alzheimer disease (AD), but it is not known whether anti-Aβ antibodies are capable of lowering oAβ levels in humans.
methodsWe developed an ultrasensitive immunoassay and used it to measure oAβ in cerebrospinal fluid (CSF) from 104 AD subjects participating in the ABBY and BLAZE phase 2 trials of the anti-Aβ antibody crenezumab. Patients received subcutaneous (SC) crenezumab (300mg) or placebo every 2 weeks, or intravenous (IV) crenezumab (15mg/kg) or placebo every 4 weeks for 68 weeks. Ninety-eight of the 104 patients had measurable baseline oAβ levels, and these were compared to levels at week 69 in placebo (n = 28), SC (n = 35), and IV (n = 35) treated patients.
resultsAmong those receiving crenezumab, 89% of SC and 86% of IV patients had lower levels of oAβ at week 69 versus baseline. The difference in the proportion of patients with decreasing levels was significant for both treatment arms: p = 0.0035 for SC and p = 0.01 for IV crenezumab versus placebo. The median percentage change was -48% in the SC arm and -43% in the IV arm. No systematic change was observed in the placebo group, with a median change of -13% and equivalent portions with negative and positive change.
interpretationCrenezumab lowered CSF oAβ levels in the large majority of treated patients tested. These results support engagement of the principal pathobiological target in AD and identify CSF oAβ as a novel pharmacodynamic biomarker for use in trials of anti-Aβ agents. ANN NEUROL 2019;86:215-224.
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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.