Cited by 431Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab

Ostrowitzki, Susanne·2012·Archives of Neurology

DOI 10.1001/archneurol.2011.1538

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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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BackgroundInfluential
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Amyloid imaging in alzheimer’s disease: A literature review
Saidlitz, P., Voisin, T., Vellas, B. J., Payoux, P., Gabelle, A., Formaglio, M., & Delrieu, J. (2014) · The journal of nutrition health & aging · doi:10.1007/s12603-014-0485-5
Pharmacological interventions in mild cognitive impairment and dementia
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Influência das Células da Glia na patogênese e progressão da Doença de Alzheimer
dos Santos, L. H. C., Neto, M. R. P., Melo, P. A. D. A. M., Oliveira, M. D. N., Monteiro, R. G. S., Lins, M. A. B., Holanda, V. C. S., Neto, A. P. C., Bezerra, A. C. S., Bonfim, E. C. C., et al. (2024) · Research Society and Development · doi:10.33448/rsd-v13i4.45475

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)
DOI: 10.1001/archneurol.2011.1538
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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Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab

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