ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
Combined treatment with a BACE inhibitor and anti-Aβ antibody gantenerumab enhances amyloid reduction in APPLondon mice.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 94 citations in OpenAlex.
- Recent advances towards BACE1 drug discovery and therapeutics design.RSC medicinal chemistry · 2026Review
- Therapeutic modulation of neurogenesis to improve hippocampal plasticity and cognition in aging and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Trends in Research on Gantenerumab for Alzheimer's Disease: A Bibliometric and Thematic Analysis.CNS & neurological disorders drug targets · 2025Article
- Proposed Therapeutic Strategy to Combat Alzheimer's Disease by Targeting Beta and Gamma Secretases.Current Alzheimer research · 2025Review
- Inhibition of BACE1 affected both its Aβ producing and degrading activities and increased Aβ42 and Aβ40 levels at high-level BACE1 expression.The Journal of biological chemistry · 2024Article
- Review on anti-alzheimer drug development: approaches, challenges and perspectives.RSC advances · 2024Review
- Transgenic amyloid precursor protein mouse models of amyloidosis. Incomplete models for Alzheimer's disease but effective predictors of anti-amyloid therapies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Review
- Review
- Diet-induced Alzheimer's-like syndrome in the rabbit.Alzheimer's & dementia (New York, N. Y.) · 2022Article
- A multitude of signaling pathways associated with Alzheimer's disease and their roles in AD pathogenesis and therapy.Medicinal research reviews · 2021Review
- The next step of neurogenesis in the context of Alzheimer's disease.Molecular biology reports · 2021Review
- Metabolic disorder in Alzheimer's disease.Metabolic brain disease · 2021Review
- Amyloid-β and α-Synuclein Immunotherapy: From Experimental Studies to Clinical Trials.Frontiers in neuroscience · 2021Review
- Computational Investigation of Gantenerumab and Crenezumab Recognition of Aβ Fibrils in Alzheimer's Disease Brain Tissue.ACS chemical neuroscience · 2020Article
- Passive immunotherapies targeting Aβ and tau in Alzheimer's disease.Neurobiology of disease · 2020Review
- Leveraging preclinical models for the development of Alzheimer disease therapeutics.Nature reviews. Drug discovery · 2020Review
- Elucidating Critical Proteinopathic Mechanisms and Potential Drug Targets in Neurodegeneration.Cellular and molecular neurobiology · 2020Review
- Novel Anti-Alzheimer's Therapeutic Molecules Targeting Amyloid Precursor Protein Processing.Oxidative medicine and cellular longevity · 2020Review
- New treatment modalities in Alzheimer's disease.World journal of clinical cases · 2019Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic approaches for prevention or reduction of amyloidosis are currently a main objective in basic and clinical research on Alzheimer's disease. Among the agents explored in clinical trials are anti-Aβ peptide antibodies and secretase inhibitors. Most anti-Aβ antibodies are considered to act via inhibition of amyloidosis and enhanced clearance of existing amyloid, although secretase inhibitors reduce the de novo production of Aβ. Limited information is currently available on the efficacy and potential advantages of combinatorial antiamyloid treatment. We performed a chronic study in APPLondon transgenic mice that received treatment with anti-Aβ antibody gantenerumab and BACE inhibitor RO5508887, either as mono- or combination treatment. Treatment aimed to evaluate efficacy on amyloid progression, similar to preexisting amyloidosis as present in Alzheimer's disease patients. Mono-treatments with either compound caused a dose-dependent reduction of total brain Aβ and amyloid burden. Combination treatment with both compounds significantly enhanced the antiamyloid effect. The observed combination effect was most pronounced for lowering of amyloid plaque load and plaque number, which suggests effective inhibition of de novo plaque formation. Moreover, significantly enhanced clearance of pre-existing amyloid plaques was observed when gantenerumab was coadministered with RO5508887. BACE inhibition led to a significant time- and dose-dependent decrease in CSF Aβ, which was not observed for gantenerumab treatment. Our results demonstrate that combining these two antiamyloid agents enhances overall efficacy and suggests that combination treatments may be of clinical relevance.
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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.