The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.
Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab
Abstract
BACKGROUND: Gantenerumab is a fully human anti-Aβ monoclonal antibody in clinical development for the treatment of Alzheimer disease (AD). OBJECTIVES: To investigate whether treatment with gantenerumab leads to a measurable reduction in the level of Aβ amyloid in the brain and to elucidate the mechanism of amyloid reduction. DESIGN: A multicenter, randomized, double-blind, placebo-controlled, ascending-dose positron emission tomographic study. Additionally, ex vivo studies of human brain slices from an independent sample of patients who had AD were performed. SETTING: Three university medical centers. PATIENTS: Patients with mild-to-moderate AD. INTERVENTION: Two consecutive cohorts of patients received 2 to 7 infusions of intravenous gantenerumab (60 or 200 mg) or placebo every 4 weeks. Brain slices from patients who had AD were coincubated with gantenerumab at increasing concentrations and with human microglial cells. MAIN OUTCOME MEASURES: Percent change in the ratio of regional carbon 11-labeled Pittsburgh Compound B retention in vivo and semiquantitative assessment of gantenerumab-induced phagocytosis ex vivo. RESULTS: Sixteen patients with end-of-treatment positron emission tomographic scans were included in the analysis. The mean (95% CI) percent change from baseline difference relative to placebo (n = 4) in cortical brain amyloid level was -15.6% (95% CI, -42.7 to 11.6) for the 60-mg group (n = 6) and -35.7% (95% CI, -63.5 to -7.9) for the 200-mg group (n = 6). Two patients in the 200-mg group showed transient and focal areas of inflammation or vasogenic edema on magnetic resonance imaging scans at sites with the highest level of amyloid reduction. Gantenerumab induced phagocytosis of human amyloid in a dose-dependent manner ex vivo. CONCLUSION: Gantenerumab treatment resulted in a dose-dependent reduction in brain amyloid level, possibly through an effector cell-mediated mechanism of action.
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“This antibody can disassemble and degrade amyloid plaques by recruiting microglia and activating phagocytosis [71,72].”
From Treatment of Alzheimer’s Disease: Beyond Symptomatic Therapies (2023) · cites this paper as [72]
In the citing paper
“Several anti-Aβ monoclonal antibodies (mAbs) have been tested in clinical trials in AD patients and were found to significantly reduce load of fibrillar Aβ as demonstrated using PET Aβ imaging [5–8].”
From APOE Genotype Differentially Modulates Effects of Anti-Aβ, Passive Immunization in APP Transgenic Mice (2017) · cites this paper as [6]
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Metadata
- Authors
- Ostrowitzki, S.
- Affiliations
- F. Hoffmann-La Roche AG (CH)
- Corresponding author
- Ostrowitzki, Susanne
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2012-02-01
- Volume
- 69
- Issue
- 2
- Pages
- 198
- ISSN
- 0003-9942 (ISSN-L)
- OpenAlex
- W2118753807
- Cited by
- 431
- References
- 19
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 34 · 2023: 22 · 2022: 22 · 2021: 24 · 2020: 18 · 2019: 23 · 2018: 30 · 2017: 34 · 2016: 39 · 2015: 31 · 2014: 44 · 2013: 45 · 2012: 24
- FWCI
- 25.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- gantenerumab, Alzheimer's disease, amyloid-beta, anti-amyloid monoclonal antibodies, phagocytosis, microglia, Pittsburgh compound B, dose-dependent effects, vasogenic edema
- MeSH terms
- Aged, Alzheimer Disease, Aniline Compounds, Antibodies, Monoclonal, Brain Chemistry, Cell Count, Double-Blind Method, Female, Follow-Up Studies, Humans, Immunoglobulin G, Injections, Intravenous, Male, Middle Aged, Phagocytosis, Thiazoles, Cohort Studies, Amyloid beta-Peptides, Microglia, Sample Size, Radiopharmaceuticals, Alzheimer Vaccines, Positron-Emission Tomography, Antibodies, Monoclonal, Humanized
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