Data-driven Stochastic Model for Quantifying the Interplay Between Amyloid-beta and Calcium Levels in Alzheimer's
Hina Shaheen1, Roderick Melnik2, Sundeep Singh3
1Faculty of Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Statistical Analysis and Data Mining
|April 22, 2024
Summary
Alzheimer's disease (AD) involves amyloid-beta and calcium dyshomeostasis. This study models the feedback loop between these factors using ADNI data, revealing how disruptions lead to AD progression and suggesting chelation therapy as a potential treatment.
Area of Science:
- Neuroscience
- Computational Biology
- Biophysics
Background:
- Alzheimer's disease (AD) is characterized by extracellular amyloid-beta aggregation and calcium dyshomeostasis.
- Intraneuronal amyloid-beta accumulation correlates with synaptic impairments, neuronal loss, and cognitive decline in AD.
- A positive feedback loop exists between amyloid-beta and calcium levels, where each exacerbates the other.
Purpose of the Study:
- To develop and analyze a novel stochastic model of the positive feedback loop between amyloid-beta and calcium in AD.
- To investigate the interplay between amyloid-beta and calcium levels across different AD disease stages using patient data.
- To explore potential therapeutic strategies targeting the balance of amyloid-beta and calcium.
Main Methods:
- Utilized a physics-based Bayesian model incorporating data from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
- Employed approximate Bayesian computation to model AD as a multi-state disease process.
- Analyzed ADNI data from 2-year patient visits to examine the interaction between amyloid-beta and calcium levels.
Main Results:
- Disruptions in amyloid-beta metabolism or intracellular calcium homeostasis significantly accelerate the relative growth rates of both amyloid-beta and calcium.
- This accelerated growth directly corresponds to the pathological development of Alzheimer's disease.
- Imbalances in calcium ions disrupt cellular processes, worsening amyloid-beta abnormalities and vice versa.
Conclusions:
- The study confirms a critical interplay between amyloid-beta and calcium dyshomeostasis in AD pathogenesis.
- Targeting the balance of calcium ions or the ratio of amyloid-beta to calcium through chelation may offer therapeutic benefits for AD.
- The findings open new avenues for research into novel Alzheimer's disease therapies.
Keywords:
Alzheimer’s diseaseBayesian inferenceCa+2 dysregulationNeurodegenrative disordersamyloid β peptideapproximate Bayesian computationdata-driven modelsfeedback mechanisms and controlneurosciencestochastic modelling
