Seyedadel Moravveji, Halima Sadia, Nicolas Doyon, Simon Duchesne
{"title":"阿尔茨海默病进展的数学模型的敏感性分析揭示了重要的因果途径。","authors":"Seyedadel Moravveji, Halima Sadia, Nicolas Doyon, Simon Duchesne","doi":"10.3389/fninf.2025.1590968","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Mathematical models serve as essential tools to investigate brain aging, the onset of Alzheimer's disease (AD) and its progression. By studying the representation of the complex dynamics of brain aging processes, such as amyloid beta (Aβ) deposition, tau tangles, neuro-inflammation, and neuronal death. Sensitivity analyses provide a powerful framework for identifying the underlying mechanisms that drive disease progression. In this study, we present the first local sensitivity analysis of a recent and comprehensive multiscale ODE-based model of Alzheimer's Disease (AD) that originates from our group. As such, it is one of the most complex model that captures the multifactorial nature of AD, incorporating neuronal, pathological, and inflammatory processes at the nano, micro and macro scales. This detailed framework enables realistic simulation of disease progression and identification of key biological parameters that influence system behavior. Our analysis identifies the key drivers of disease progression across patient profiles, providing insight into targeted therapeutic strategies.</p><p><strong>Methods: </strong>We investigated a recent ODE-based model composed of 19 variables and 75 parameters, developed by our group, to study Alzheimer's disease dynamics. We performed single- and paired-parameter sensitivity analyses, focusing on three key outcomes: neural density, amyloid beta plaques, and tau proteins.</p><p><strong>Results: </strong>Our findings suggest that the parameters related to glucose and insulin regulation could play an important role in neurodegeneration and cognitive decline. Second, the parameters that have the most important impact on cognitive decline are not completely the same depending on sex and APOE status.</p><p><strong>Discussion: </strong>These results underscore the importance of incorporating a multifactorial approach tailored to demographic characteristics when considering strategies for AD treatment. This approach is essential to identify the factors that contribute significantly to neural loss and AD progression.</p>","PeriodicalId":12462,"journal":{"name":"Frontiers in Neuroinformatics","volume":"19 ","pages":"1590968"},"PeriodicalIF":2.5000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325246/pdf/","citationCount":"0","resultStr":"{\"title\":\"Sensitivity analysis of a mathematical model of Alzheimer's disease progression unveils important causal pathways.\",\"authors\":\"Seyedadel Moravveji, Halima Sadia, Nicolas Doyon, Simon Duchesne\",\"doi\":\"10.3389/fninf.2025.1590968\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Mathematical models serve as essential tools to investigate brain aging, the onset of Alzheimer's disease (AD) and its progression. By studying the representation of the complex dynamics of brain aging processes, such as amyloid beta (Aβ) deposition, tau tangles, neuro-inflammation, and neuronal death. Sensitivity analyses provide a powerful framework for identifying the underlying mechanisms that drive disease progression. In this study, we present the first local sensitivity analysis of a recent and comprehensive multiscale ODE-based model of Alzheimer's Disease (AD) that originates from our group. As such, it is one of the most complex model that captures the multifactorial nature of AD, incorporating neuronal, pathological, and inflammatory processes at the nano, micro and macro scales. This detailed framework enables realistic simulation of disease progression and identification of key biological parameters that influence system behavior. Our analysis identifies the key drivers of disease progression across patient profiles, providing insight into targeted therapeutic strategies.</p><p><strong>Methods: </strong>We investigated a recent ODE-based model composed of 19 variables and 75 parameters, developed by our group, to study Alzheimer's disease dynamics. We performed single- and paired-parameter sensitivity analyses, focusing on three key outcomes: neural density, amyloid beta plaques, and tau proteins.</p><p><strong>Results: </strong>Our findings suggest that the parameters related to glucose and insulin regulation could play an important role in neurodegeneration and cognitive decline. Second, the parameters that have the most important impact on cognitive decline are not completely the same depending on sex and APOE status.</p><p><strong>Discussion: </strong>These results underscore the importance of incorporating a multifactorial approach tailored to demographic characteristics when considering strategies for AD treatment. This approach is essential to identify the factors that contribute significantly to neural loss and AD progression.</p>\",\"PeriodicalId\":12462,\"journal\":{\"name\":\"Frontiers in Neuroinformatics\",\"volume\":\"19 \",\"pages\":\"1590968\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2025-07-23\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12325246/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Neuroinformatics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fninf.2025.1590968\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"MATHEMATICAL & COMPUTATIONAL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Neuroinformatics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fninf.2025.1590968","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MATHEMATICAL & COMPUTATIONAL BIOLOGY","Score":null,"Total":0}
Sensitivity analysis of a mathematical model of Alzheimer's disease progression unveils important causal pathways.
Introduction: Mathematical models serve as essential tools to investigate brain aging, the onset of Alzheimer's disease (AD) and its progression. By studying the representation of the complex dynamics of brain aging processes, such as amyloid beta (Aβ) deposition, tau tangles, neuro-inflammation, and neuronal death. Sensitivity analyses provide a powerful framework for identifying the underlying mechanisms that drive disease progression. In this study, we present the first local sensitivity analysis of a recent and comprehensive multiscale ODE-based model of Alzheimer's Disease (AD) that originates from our group. As such, it is one of the most complex model that captures the multifactorial nature of AD, incorporating neuronal, pathological, and inflammatory processes at the nano, micro and macro scales. This detailed framework enables realistic simulation of disease progression and identification of key biological parameters that influence system behavior. Our analysis identifies the key drivers of disease progression across patient profiles, providing insight into targeted therapeutic strategies.
Methods: We investigated a recent ODE-based model composed of 19 variables and 75 parameters, developed by our group, to study Alzheimer's disease dynamics. We performed single- and paired-parameter sensitivity analyses, focusing on three key outcomes: neural density, amyloid beta plaques, and tau proteins.
Results: Our findings suggest that the parameters related to glucose and insulin regulation could play an important role in neurodegeneration and cognitive decline. Second, the parameters that have the most important impact on cognitive decline are not completely the same depending on sex and APOE status.
Discussion: These results underscore the importance of incorporating a multifactorial approach tailored to demographic characteristics when considering strategies for AD treatment. This approach is essential to identify the factors that contribute significantly to neural loss and AD progression.
期刊介绍：
Frontiers in Neuroinformatics publishes rigorously peer-reviewed research on the development and implementation of numerical/computational models and analytical tools used to share, integrate and analyze experimental data and advance theories of the nervous system functions. Specialty Chief Editors Jan G. Bjaalie at the University of Oslo and Sean L. Hill at the École Polytechnique Fédérale de Lausanne are supported by an outstanding Editorial Board of international experts. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics and the public worldwide.
Neuroscience is being propelled into the information age as the volume of information explodes, demanding organization and synthesis. Novel synthesis approaches are opening up a new dimension for the exploration of the components of brain elements and systems and the vast number of variables that underlie their functions. Neural data is highly heterogeneous with complex inter-relations across multiple levels, driving the need for innovative organizing and synthesizing approaches from genes to cognition, and covering a range of species and disease states.
Frontiers in Neuroinformatics therefore welcomes submissions on existing neuroscience databases, development of data and knowledge bases for all levels of neuroscience, applications and technologies that can facilitate data sharing (interoperability, formats, terminologies, and ontologies), and novel tools for data acquisition, analyses, visualization, and dissemination of nervous system data. Our journal welcomes submissions on new tools (software and hardware) that support brain modeling, and the merging of neuroscience databases with brain models used for simulation and visualization.
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