Department of Mechanical Engineering, Stevens Institute of Technology, Hoboken, New Jersey 07030, USA.
Living Matter Laboratory, Stanford University, Stanford, California 94305, USA.
Phys Rev Lett. 2018 Oct 12;121(15):158101. doi: 10.1103/PhysRevLett.121.158101.
Many neurodegenerative diseases are related to the propagation and accumulation of toxic proteins throughout the brain. The lesions created by aggregates of these toxic proteins further lead to cell death and accelerated tissue atrophy. A striking feature of some of these diseases is their characteristic pattern and evolution, leading to well-codified disease stages visible to neuropathology and associated with various cognitive deficits and pathologies. Here, we simulate the anisotropic propagation and accumulation of toxic proteins in full brain geometry. We show that the same model with different initial seeding zones reproduces the characteristic evolution of different prionlike diseases. We also recover the expected evolution of the total toxic protein load. Finally, we couple our transport model to a mechanical atrophy model to obtain the typical degeneration patterns found in neurodegenerative diseases.
许多神经退行性疾病都与有毒蛋白质在整个大脑中的传播和积累有关。这些有毒蛋白质聚集体造成的损伤进一步导致细胞死亡和组织加速萎缩。这些疾病的一个显著特征是其特征性的模式和演变,导致神经病理学可见的明确的疾病阶段,并与各种认知缺陷和病变相关。在这里,我们模拟有毒蛋白质在全脑几何形状中的各向异性传播和积累。我们表明,具有不同初始播种区的相同模型再现了不同朊病毒样疾病的特征演变。我们还恢复了总有毒蛋白质负荷的预期演变。最后,我们将我们的传输模型与机械萎缩模型耦合,以获得神经退行性疾病中发现的典型退化模式。