Spatially-extended nucleation-aggregation-fragmentation models for the dynamics of prion-like neurodegenerative protein-spreading in the brain and its connectome
| Autor: | Amelie Schäfer, Ellen Kuhl, Sveva Fornari, Alain Goriely |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Statistics and Probability Prions Nucleation tau Proteins General Biochemistry Genetics and Molecular Biology Tissue death 03 medical and health sciences 0302 clinical medicine Connectome Humans Cognitive decline Prion protein 030304 developmental biology 0303 health sciences Amyloid beta-Peptides General Immunology and Microbiology Chemistry Applied Mathematics Dynamics (mechanics) Fragmentation (computing) Brain Neurodegenerative Diseases General Medicine 030104 developmental biology Modeling and Simulation Biophysics Protein folding General Agricultural and Biological Sciences 030217 neurology & neurosurgery |
| DOI: | 10.1101/692038 |
| Popis: | The prion-like hypothesis of neurodegenerative diseases states that the accumulation of misfolded proteins in the form of aggregates is responsible for tissue death and its associated neurodegenerative pathology and cognitive decline. Some disease-specific misfolded proteins can interact with healthy proteins to form long chains that are transported through the brain along axonal pathways. Since aggregates of different sizes have different transport properties and toxicity, it is important to follow independently their evolution in space and time. Here, we model the spreading and propagation of aggregates of misfolded proteins in the brain using the general Smoluchowski theory of nucleation, aggregation, and fragmentation. The transport processes considered here are either anisotropic diffusion along axonal bundles or discrete Laplacian transport along a network. In particular, we model the spreading and aggregation of both amyloid-β and τ molecules in the brain connectome. We show that these two models lead to different size distributions and different propagation along the network. A detailed analysis of these two models reveals the existence of four different stages with different dynamics and invasive properties. |
| Databáze: | OpenAIRE |
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