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一种纳米、微米和宏观尺度下的阿尔茨海默病计算模型。

A computational model of Alzheimer's disease at the nano, micro, and macroscales.

作者信息

Chamberland Éléonore, Moravveji Seyedadel, Doyon Nicolas, Duchesne Simon

机构信息

Centre de Recherche CERVO, Institut Universitaire de Santé Mentale de Québec, Québec, QC, Canada.

Département de Mathématiques et de Statistique, Québec, QC, Canada.

出版信息

Front Neuroinform. 2024 Mar 22;18:1348113. doi: 10.3389/fninf.2024.1348113. eCollection 2024.

Abstract

INTRODUCTION

Mathematical models play a crucial role in investigating complex biological systems, enabling a comprehensive understanding of interactions among various components and facilitating testing of intervention strategies. Alzheimer's disease (AD) is characterized by multifactorial causes and intricate interactions among biological entities, necessitating a personalized approach due to the lack of effective treatments. Therefore, mathematical models offer promise as indispensable tools in combating AD. However, existing models in this emerging field often suffer from limitations such as inadequate validation or a narrow focus on single proteins or pathways.

METHODS

In this paper, we present a multiscale mathematical model that describes the progression of AD through a system of 19 ordinary differential equations. The equations describe the evolution of proteins (nanoscale), cell populations (microscale), and organ-level structures (macroscale) over a 50-year lifespan, as they relate to amyloid and tau accumulation, inflammation, and neuronal death.

RESULTS

Distinguishing our model is a robust foundation in biological principles, ensuring improved justification for the included equations, and rigorous parameter justification derived from published experimental literature.

CONCLUSION

This model represents an essential initial step toward constructing a predictive framework, which holds significant potential for identifying effective therapeutic targets in the fight against AD.

摘要

引言

数学模型在研究复杂生物系统中起着至关重要的作用,能够全面理解各组成部分之间的相互作用,并有助于测试干预策略。阿尔茨海默病(AD)具有多因素病因以及生物实体之间复杂的相互作用,由于缺乏有效的治疗方法,需要采用个性化方法。因此,数学模型有望成为对抗AD不可或缺的工具。然而,这个新兴领域中的现有模型常常存在局限性,例如验证不足或仅狭隘地关注单一蛋白质或信号通路。

方法

在本文中,我们提出了一个多尺度数学模型,该模型通过一个由19个常微分方程组成的系统来描述AD的进展。这些方程描述了在50年的生命周期内蛋白质(纳米尺度)、细胞群体(微观尺度)和器官水平结构(宏观尺度)的演变,因为它们与淀粉样蛋白和tau蛋白的积累、炎症以及神经元死亡有关。

结果

我们模型的独特之处在于其基于生物学原理的坚实基础,确保了所包含方程有更好的合理性,以及从已发表的实验文献中得出的严格参数论证。

结论

该模型是构建预测框架的重要初始步骤,在确定对抗AD的有效治疗靶点方面具有巨大潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2868/10995318/26832bee1640/fninf-18-1348113-g0001.jpg

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