ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2021
Systematic in silico analysis of clinically tested drugs for reducing amyloid-beta plaque accumulation in Alzheimer's disease.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Quantitative Systems Pharmacology Models of Anti-Amyloid Treatments for Alzheimer's Disease: A Systematic Review.CPT: pharmacometrics & systems pharmacology · 2026Pooled it
- Recent applications of quantitative systems pharmacology and machine learning models across diseases.Journal of pharmacokinetics and pharmacodynamics · 2022Pooled it
- Trial
- Engineered mesenchymal stem cell-derived extracellular vesicles overexpressing miR-146a alleviate neuroinflammation in Alzheimer's disease.Neural regeneration research · 2026Article
- Mechanistic modeling of amyloid dynamics relating to Alzheimer's disease progression.Frontiers in aging neuroscience · 2026Article
- The role for artificial intelligence in identifying combination therapies for Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Review
- Translatability of Animal Models for Alzheimer's Disease Using a Machine Learning Based Workflow.Clinical and translational science · 2025Article
- Second-generation anti-amyloid monoclonal antibodies for Alzheimer's disease: current landscape and future perspectives.Translational neurodegeneration · 2025Review
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Molecular and Cellular Foundations of Aging of the Brain: Anti-aging Strategies in Alzheimer's Disease.Cellular and molecular neurobiology · 2024Review
- Computational neurosciences and quantitative systems pharmacology: a powerful combination for supporting drug development in neurodegenerative diseases.Journal of pharmacokinetics and pharmacodynamics · 2024Review
- Stress-mediated aggregation of disease-associated proteins in amyloid bodies.Scientific reports · 2023Article
- Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model.Scientific reports · 2023Article
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
- Clinical relevance of animal models in aging-related dementia research.Nature aging · 2023Review
- A combined physiologically-based pharmacokinetic and quantitative systems pharmacology model for modeling amyloid aggregation in Alzheimer's disease.CPT: pharmacometrics & systems pharmacology · 2023Article
- Quantitative systems pharmacology model of the amyloid pathway in Alzheimer's disease: Insights into the therapeutic mechanisms of clinical candidates.CPT: pharmacometrics & systems pharmacology · 2023Article
- Mathematical model of mechanobiology of acute and repeated synaptic injury and systemic biomarker kinetics.Frontiers in cellular neuroscience · 2023Article
- Hallmarks of neurodegenerative disease: A systems pharmacology perspective.CPT: pharmacometrics & systems pharmacology · 2022Review
- Quantitative Systems Pharmacology and Biased Agonism at Opioid Receptors: A Potential Avenue for Improved Analgesics.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
introductionDespite strong evidence linking amyloid beta (Aβ) to Alzheimer's disease, most clinical trials have shown no clinical efficacy for reasons that remain unclear. To understand why, we developed a quantitative systems pharmacology (QSP) model for seven therapeutics: aducanumab, crenezumab, solanezumab, bapineuzumab, elenbecestat, verubecestat, and semagacestat.
methodsOrdinary differential equations were used to model the production, transport, and aggregation of Aβ; pharmacology of the drugs; and their impact on plaque.
resultsThe calibrated model predicts that endogenous plaque turnover is slow, with an estimated half-life of 2.75 years. This is likely why beta-secretase inhibitors have a smaller effect on plaque reduction. Of the mechanisms tested, the model predicts binding to plaque and inducing antibody-dependent cellular phagocytosis is the best approach for plaque reduction. DISCUSSION: A QSP model can provide novel insights to clinical results. Our model explains the results of clinical trials and provides guidance for future therapeutic development.
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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.