Adaptive modelling of anti-tau treatments for neurodegenerative disorders based on the Bayesian approach with physics-informed neural networks

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Hauptverfasser: Pal, Swadesh, Melnik, Roderick
Format: Preprint
Veröffentlicht: 2025
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author Pal, Swadesh
Melnik, Roderick
author_facet Pal, Swadesh
Melnik, Roderick
contents Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of amyloid-beta (A$β$) and phosphorylated tau (p-tau) proteins, leading to cognitive decline measured by the Alzheimer's Disease Assessment Scale (ADAS) score. In this study, we develop and analyze a system of ordinary differential equation models to describe the interactions between A$β$, p-tau, and ADAS score, providing a mechanistic understanding of disease progression. To ensure accurate model calibration, we employ Bayesian inference and Physics-Informed Neural Networks (PINNs) for parameter estimation based on Alzheimer's Disease Neuroimaging Initiative data. The data-driven Bayesian approach enables uncertainty quantification, improving confidence in model predictions, while the PINN framework leverages neural networks to capture complex dynamics directly from data. Furthermore, we implement an optimal control strategy to assess the efficacy of an anti-tau therapeutic intervention aimed at reducing p-tau levels and mitigating cognitive decline. Our data-driven solutions indicate that while optimal drug administration effectively decreases p-tau concentration, its impact on cognitive decline, as reflected in the ADAS score, remains limited. These findings suggest that targeting p-tau alone may not be sufficient for significant cognitive improvement, highlighting the need for multi-target therapeutic strategies. The integration of mechanistic modelling, advanced parameter estimation, and control-based therapeutic optimization provides a comprehensive framework for improving treatment strategies for AD.
format Preprint
id arxiv_https___arxiv_org_abs_2504_13438
institution arXiv
publishDate 2025
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spellingShingle Adaptive modelling of anti-tau treatments for neurodegenerative disorders based on the Bayesian approach with physics-informed neural networks
Pal, Swadesh
Melnik, Roderick
Neurons and Cognition
Quantitative Methods
Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by the accumulation of amyloid-beta (A$β$) and phosphorylated tau (p-tau) proteins, leading to cognitive decline measured by the Alzheimer's Disease Assessment Scale (ADAS) score. In this study, we develop and analyze a system of ordinary differential equation models to describe the interactions between A$β$, p-tau, and ADAS score, providing a mechanistic understanding of disease progression. To ensure accurate model calibration, we employ Bayesian inference and Physics-Informed Neural Networks (PINNs) for parameter estimation based on Alzheimer's Disease Neuroimaging Initiative data. The data-driven Bayesian approach enables uncertainty quantification, improving confidence in model predictions, while the PINN framework leverages neural networks to capture complex dynamics directly from data. Furthermore, we implement an optimal control strategy to assess the efficacy of an anti-tau therapeutic intervention aimed at reducing p-tau levels and mitigating cognitive decline. Our data-driven solutions indicate that while optimal drug administration effectively decreases p-tau concentration, its impact on cognitive decline, as reflected in the ADAS score, remains limited. These findings suggest that targeting p-tau alone may not be sufficient for significant cognitive improvement, highlighting the need for multi-target therapeutic strategies. The integration of mechanistic modelling, advanced parameter estimation, and control-based therapeutic optimization provides a comprehensive framework for improving treatment strategies for AD.
title Adaptive modelling of anti-tau treatments for neurodegenerative disorders based on the Bayesian approach with physics-informed neural networks
topic Neurons and Cognition
Quantitative Methods
url https://arxiv.org/abs/2504.13438