| Issue |
ESAIM: ProcS
Volume 67, 2020
CEMRACS 2018 - Numerical and mathematical modeling for biological and medical applications: deterministic, probabilistic and statistical descriptions
|
|
|---|---|---|
| Page(s) | 30 - 45 | |
| DOI | https://doi.org/10.1051/proc/202067003 | |
| Published online | 09 June 2020 | |
Modeling the spatial propagation of Aβ oligomers in Alzheimer’s Disease
1 Institut Jacques Monod, CNRS UMR 7592, Université Paris Diderot, Paris Cité Sorbonne, F-750205, Paris, France
2 Institut Camille Jordan, Université de Lyon, Université Claude Bernard Lyon 1, CNRS UMR 5208, 43 blvd. du 11 novembre 1918, 69622 Villeurbanne cedex, France
3 Team Dracula, INRIA, 69603 Villeurbanne Cedex, France
Recent advances in the study of Alzheimer’s Disease and the role of Aβ amyloid formation have caused the focus of biologists to progressively shift towards the smaller protein assemblies, the oligomers. These appear very early on in the disease progression and they seem to be the most infectious species for the neurons. We suggest a model of spatial propagation of Aβ oligomers in the vicinity of a few neurons, without considering the formation of large fibrils or plaques. We also include a simple representation of the oligomers neurotoxic effect. A numerical study reveals that the oligomers spatial dynamics are very sensitive to the balance between their diffusion and their replication, and that the outcome in terms of the progression of AD strongly depends on it.
Résumé
Au cours des dernières années, la recherche sur la maladie d’Alzheimer a révélé l’importance des oligomères d’Aβ dans le développement de la pathologie. Ces structures de petite taille, en comparaison aux fibrilles et aux plaques amyloïdes, apparaissent au cours des toutes premières étapes de la maladie et semblent être les espèces les plus toxiques pour les neurones. En conséquence, nous proposons un modèle de propagation spatiale des oligomères dans le voisinage de quelques neurones, sans considérer la présence de plus grandes structures. La toxicité des oligomères est aussi modélisée de faҫon simplifiée. L’étude numérique de ce modèle nous permet de mettre en évidence l’influence critique de l’équilibre entre diffusion et réplication des oligomères sur leur répartition spatiale, et la progression de la maladie d’Alzheimer en dépend fortement.
© EDP Sciences, SMAI 2020
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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