P1–114: Changes in calcium‐related gene expression consistent with Alzheimer's disease are initiated by infection of neuronal cells with <i>Chlamydia pneumoniae</i>

Appelt, Denah M.; Cappellini, Christopher A.; Cader, Ahmad; Williams, K.G.; Hingley, Susan T.; Bell, Marcus G.; Balin, Brian J.

doi:10.1016/j.jalz.2013.05.336

Cited by 2 publications

(1 citation statement)

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“…In fact, bacterial initiation may be linked to the abnormal gene expression seen in AD. One study found that C. pneumoniae possibly causes the dysfunctional AD calcium-related gene expression: human neuronal cells injected with the microbes exhibited similar gene expression as brain cells from AD patients [13]. However, it is important to note that AD may not have a single cause but is rather a result of multiple factors [1].…”

Section: Introductionmentioning

confidence: 99%

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

Sundar

Battistoni

McNulty

et al. 2020

Theor Biol Med Model

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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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Section: Introductionmentioning

confidence: 99%