一种用于预测阿尔茨海默病传播的计算框架
A computational framework to predict the spreading of Alzheimer's disease
AI总结：
本文提出一种三维有限元框架，结合多蛋白运输和脑组织变形，模拟阿尔茨海默病的进展，通过反应扩散方程描述有毒tau和淀粉样蛋白的传播，并展示与纵向影像测量的良好一致性。
摘要：
阿尔茨海默病的特点是错误折叠蛋白质的传播和大脑的逐步结构变化。尽管有大量临床研究，理解微观蛋白质动力学如何转化为宏观组织退化仍然是重大挑战。本文提出了一种三维、基于有限元的计算框架，通过结合多蛋白运输和脑组织变形，模拟疾病进展。有毒tau和淀粉样蛋白的传播通过鱼尔-科尔莫戈罗夫类型的反应扩散方程描述，结合类似朊病毒的生长机制和沿白质纤维束的各向异性运输。脑萎缩通过由蛋白质依赖体积损失驱动的超弹性本构模型表示。通过自动化预处理管道实现受体特异性模拟，该管道生成有限元网格并从医学影像数据中重建轴突取向场。该模型重现了阿尔茨海默病观察到的关键形态模式，并与纵向影像测量表现出良好的定量一致性。总体而言，所提出的框架提供了一个可扩展的计算平台，用于研究阿尔茨海默病在受体特异性脑几何结构上的进展。开发的模型，包括图像处理框架（BrainImage2Mesh）和耦合生物-化学-机械的COMSOL有限元实现，已免费提供下载，网址为https://mechmat.web.ox.ac.uk/codes。
英文摘要：
Alzheimer's disease is characterised by the spreading of misfolded proteins and progressive structural changes in the brain. Despite significant clinical research, understanding how microscopic protein dynamics translate into macroscopic tissue degeneration remains a major challenge. In this work, we present a three-dimensional, finite element-based computational framework to model disease progression by combining multi-protein transport and brain tissue deformation within anatomically realistic geometries. The propagation of toxic tau and amyloid-beta proteins is described using reaction-diffusion equations of the Fisher-Kolmogorov type, incorporating prion-like growth mechanisms and anisotropic transport along white matter fibre tracts. Brain atrophy is represented through a hyperelastic constitutive model driven by protein-dependent volume loss. Subject-specific simulations are achieved through an automated preprocessing pipeline that generates finite element meshes and reconstructs axonal orientation fields from medical imaging data. The model reproduces key morphological patterns observed in Alzheimer's disease and shows good quantitative agreement with longitudinal imaging measurements. Overall, the proposed framework offers an extensible computational platform for studying Alzheimer's disease progression across subject-specific brain geometries. The models developed, including the image processing framework (BrainImage2Mesh) and the coupled bio-chemo-mechanical COMSOL finite element implementation, are made freely available to download at https://mechmat.web.ox.ac.uk/codes.
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