一个基于主体的模型研究微生物通过嗅觉系统引发阿尔茨海默病。

Q1 Mathematics
Shalini Sundar, Carly Battistoni, Ryan McNulty, Fernando Morales, Jonathan Gorky, Henry Foley, Prasad Dhurjati
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引用次数: 5

摘要

背景:阿尔茨海默病(AD)是一种退行性脑疾病。在NetLogo 3D中开发了一种新的基于代理的建模框架,以提供对微生物(例如细菌)的潜在机制的基本见解。肺炎衣原体可能在迟发性AD中起作用。我们最初模型的目的是模拟细菌通过嗅觉系统传播的一种可能的空间和时间途径,这可能导致AD症状。该模型描绘了细菌从鼻腔和嗅上皮感染细胞,通过嗅球进入大脑的嗅皮层和海马区。结果:基于一套生物学规则,模拟随机感染的微生物导致β -淀粉样蛋白(Aβ)斑块和神经原纤维(NF)缠结的形成,并引起免疫反应。我们的初步模拟表明,吸入肺炎球菌可导致感染传播,并在嗅皮质和海马中显著积聚Aβ斑块和NF缠结。我们的模型还显示了粘膜和神经免疫如何在考虑的途径中发挥重要作用。免疫力较低与老年人相关,他们的β斑块和NF缠结形成计数更快、更多。相比之下,与年轻个体相关的较高免疫力几乎没有这种形成。结论:该模型框架为阿尔茨海默病如何通过嗅觉系统发生进展提供了有组织的视觉表现,从而更好地了解疾病的发病机制。该模型证实了现有研究中的当前结论,但可以很容易地进行调整,以匹配未来的证据,并被研究人员用于他们自己的个人目的。我们最初模型的目标是最终指导进一步的假设完善和实验测试,以更好地了解AD病因和发病机制中存在的动态系统相互作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

An agent-based model to investigate microbial initiation of Alzheimer's via the olfactory system.

An agent-based model to investigate microbial initiation of Alzheimer's via the olfactory system.

An agent-based model to investigate microbial initiation of Alzheimer's via the olfactory system.

An agent-based model to investigate microbial initiation of Alzheimer's via the olfactory system.

Background: Alzheimer's disease (AD) is a degenerative brain disease. A novel agent-based modelling framework was developed in NetLogo 3D to provide fundamental insights into the potential mechanisms by which a microbe (eg. Chlamydia pneumoniae) may play a role in late-onset AD. The objective of our initial model is to simulate one possible spatial and temporal pathway of bacterial propagation via the olfactory system, which may then lead to AD symptoms. The model maps the bacteria infecting cells from the nasal cavity and the olfactory epithelium, through the olfactory bulb and into the olfactory cortex and hippocampus regions of the brain.

Results: Based on the set of biological rules, simulated randomized infection by the microbe led to the formation of beta-amyloid (Aβ) plaque and neurofibrillary (NF) tangles as well as caused immune responses. Our initial simulations demonstrated that breathing in C. pneumoniae can result in infection propagation and significant buildup of Aβ plaque and NF tangles in the olfactory cortex and hippocampus. Our model also indicated how mucosal and neural immunity can play a significant role in the pathway considered. Lower immunities, correlated with elderly individuals, had quicker and more Aβ plaque and NF tangle formation counts. In contrast, higher immunities, correlated with younger individuals, demonstrated little to no such formation.

Conclusion: The modelling framework provides an organized visual representation of how AD progression may occur via the olfactory system to better understand disease pathogenesis. The model confirms current conclusions in available research but can be easily adjusted to match future evidence and be used by researchers for their own individual purposes. The goal of our initial model is to ultimately guide further hypothesis refinement and experimental testing to better understand the dynamic system interactions present in the etiology and pathogenesis of AD.

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来源期刊
Theoretical Biology and Medical Modelling
Theoretical Biology and Medical Modelling MATHEMATICAL & COMPUTATIONAL BIOLOGY-
自引率
0.00%
发文量
0
审稿时长
6-12 weeks
期刊介绍: Theoretical Biology and Medical Modelling is an open access peer-reviewed journal adopting a broad definition of "biology" and focusing on theoretical ideas and models associated with developments in biology and medicine. Mathematicians, biologists and clinicians of various specialisms, philosophers and historians of science are all contributing to the emergence of novel concepts in an age of systems biology, bioinformatics and computer modelling. This is the field in which Theoretical Biology and Medical Modelling operates. We welcome submissions that are technically sound and offering either improved understanding in biology and medicine or progress in theory or method.
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