Abstract
BackgroundAlzheimer’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.ResultsBased 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.ConclusionThe 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.
Highlights
Alzheimer’s disease (AD) is a degenerative brain disease
We have developed an agent-based computational framework in NetLogo 3D to model the possible precursor steps wherein C. pneumoniae may lead to late-onset AD development via the olfactory system [14]
elementary body (EB) of C. pneumoniae can be introduced into the system by flipping the C-Pneumoniae-Exposure switch to “on”
Summary
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 In 2012, The National Alzheimer’s Plan was released to outline an approach for more effective prevention methods by 2025 [4]. Despite such efforts, AD is not completely understood, and treatment modalities have yet to yield remission or halt progression. This has, in turn, motivated comprehensive investigations into new avenues of research such as the use of personalized biomarker tests [1]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call