ArticleAlzheimer's research & therapy2012
Simulations of symptomatic treatments for Alzheimer's disease: computational analysis of pathology and mechanisms of drug action.
Article in Alzheimer's research & therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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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.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Understanding quantitative effects of anti-amyloid therapies on tau biomarkers and functional outcome. Insights from a comprehensive mechanistic quantitative systems pharmacology study.Frontiers in pharmacology · 2026Article
- Quantitative Systems Pharmacology Development and Application in Neuroscience.Handbook of experimental pharmacology · 2025Review
- Building a knowledge graph to enable precision medicine.Scientific data · 2023Article
- Gender Differences in Demographic and Pharmacological Factors in Patients Diagnosed with Late-Onset of Alzheimer's Disease.Brain sciences · 2022Article
- Research trends and hotspots of neurodegenerative diseases employing network pharmacology: A bibliometric analysis.Frontiers in pharmacology · 2022Article
- Modeling Neurotransmission: Computational Tools to Investigate Neurological Disorders.International journal of molecular sciences · 2021Review
- Computational Approaches for Supporting Combination Therapy in the Post-Aducanumab Era in Alzheimer's Disease.Journal of Alzheimer's disease reports · 2021Review
- Toward Predicting Impact of Common Genetic Variants on Schizophrenia Clinical Responses With Antipsychotics: A Quantitative System Pharmacology Study.Frontiers in neuroscience · 2021Article
- Intepirdine as adjunctive therapy to donepezil for mild-to-moderate Alzheimer's disease: A randomized, placebo-controlled, phase 3 clinical trial (MINDSET).Alzheimer's & dementia (New York, N. Y.) · 2021Article
- Learning from amyloid trials in Alzheimer's disease. A virtual patient analysis using a quantitative systems pharmacology approach.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020Article
- Quantitative Systems Pharmacology for Neuroscience Drug Discovery and Development: Current Status, Opportunities, and Challenges.CPT: pharmacometrics & systems pharmacology · 2020Article
- A modeling informed quantitative approach to salvage clinical trials interrupted due to COVID-19.Alzheimer's & dementia (New York, N. Y.) · 2020Article
- When Does Alzheimer's Disease Really Start? The Role of Biomarkers.International journal of molecular sciences · 2019Review
- Neuronal Circuit-Based Computer Modeling as a Phenotypic Strategy for CNS R&D.Frontiers in neuroscience · 2019Article
- Computational modeling and biomarker studies of pharmacological treatment of Alzheimer's disease (Review).Molecular medicine reports · 2018Review
- Impact of amyloid-beta changes on cognitive outcomes in Alzheimer's disease: analysis of clinical trials using a quantitative systems pharmacology model.Alzheimer's research & therapy · 2018Article
- A physical model for dementia.Physica A · 2017Article
- A Humanized Clinically Calibrated Quantitative Systems Pharmacology Model for Hypokinetic Motor Symptoms in Parkinson's Disease.Frontiers in pharmacology · 2016Article
- Assessing the synergy between cholinomimetics and memantine as augmentation therapy in cognitive impairment in schizophrenia. A virtual human patient trial using quantitative systems pharmacology.Frontiers in pharmacology · 2015Article
- A computer-based quantitative systems pharmacology model of negative symptoms in schizophrenia: exploring glycine modulation of excitation-inhibition balance.Frontiers in pharmacology · 2014Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionA substantial number of therapeutic drugs for Alzheimer's disease (AD) have failed in late-stage trials, highlighting the translational disconnect with pathology-based animal models.
methodsTo bridge the gap between preclinical animal models and clinical outcomes, we implemented a conductance-based computational model of cortical circuitry to simulate working memory as a measure for cognitive function. The model was initially calibrated using preclinical data on receptor pharmacology of catecholamine and cholinergic neurotransmitters. The pathology of AD was subsequently implemented as synaptic and neuronal loss and a decrease in cholinergic tone. The model was further calibrated with clinical Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) results on acetylcholinesterase inhibitors and 5-HT6 antagonists to improve the model's prediction of clinical outcomes.
resultsAs an independent validation, we reproduced clinical data for apolipoprotein E (APOE) genotypes showing that the ApoE4 genotype reduces the network performance much more in mild cognitive impairment conditions than at later stages of AD pathology. We then demonstrated the differential effect of memantine, an N-Methyl-D-aspartic acid (NMDA) subunit selective weak inhibitor, in early and late AD pathology, and show that inhibition of the NMDA receptor NR2C/NR2D subunits located on inhibitory interneurons compensates for the greater excitatory decline observed with pathology.
conclusionsThis quantitative systems pharmacology approach is shown to be complementary to traditional animal models, with the potential to assess potential off-target effects, the consequences of pharmacologically active human metabolites, the effect of comedications, and the impact of a small number of well described genotypes.
Identifiers
What OpenQuestion holds
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.