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.

中文翻译：

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一种基于代理的模型，用于研究微生物通过嗅觉系统引发阿尔茨海默病。

背景技术阿尔茨海默病(AD)是一种退行性脑部疾病。NetLogo 3D 开发了一种新颖的基于代理的建模框架，为微生物（例如肺炎衣原体）在迟发性 AD 中发挥作用的潜在机制提供基本见解。我们最初模型的目标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，这可能会导致 AD 症状。该模型描绘了从鼻腔和嗅觉上皮细胞感染细胞，通过嗅球进入大脑嗅皮层和海马区的细菌。结果根据一组生物学规则，微生物的模拟随机感染导致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。我们最初的模拟表明，吸入肺炎衣原体会导致感染传播，并导致嗅觉皮层和海马中 Aβ 斑块和 NF 缠结的显着积聚。我们的模型还表明粘膜和神经免疫如何在所考虑的途径中发挥重要作用。与老年人相关的免疫力较低，Aβ 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表现出这种形成。结论 该建模框架提供了 AD 如何通过嗅觉系统进展的有组织的视觉表示，以更好地了解疾病发病机制。该模型证实了现有研究中的当前结论，但可以轻松调整以匹配未来的证据，并可供研究人员用于自己的个人目的。我们初始模型的目标是最终指导进一步的假设细化和实验测试，以更好地理解 AD 病因和发病机制中存在的动态系统相互作用。