Computational model to study misfolded protein dynamics in the brain
November 2014
Montreal Neurological Institute, Montreal, Canada
The aggregation of misfolded proteins is associated with several neuropathologies. Amyloid-beta is one of them, and its mechanisms of propagation and deposition are not well understood. In this study, a computational approach is used to generate an epidemic spreading model for misfolded protein dynamics that reconstructs individual lifetime intra-brain propagation and the factors that promote it. Using PET amyloid-beta datasets, the model was able to reproduce amyloid-beta deposition patterns in human brains and proposes several mechanisms that explain the amyloid beta-driven onset and progression in Alzheimer's disease, but also its deposition's dynamics in the normal ageing brain. It was also capable of relating the accumulation of amyloid-beta to several other factors and the interactions between them. In summary, this model allows to relate misfolded protein dynamics in the brain with individual risk factors and clinical and demographic data, opening the door to explore the mechanisms of misfolded proteins associated with ageing and neurological pathologies.
Epidemic spreading model to characterize misfolded proteins propagation in aging and associated neurodegenerative disorders
Yasser Iturria-Medina, Alan C. Evans
Added on: 08-08-2021
[1] https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003956[2] https://data.jrc.ec.europa.eu/dataset/a8fd26ef-b113-47ab-92ba-fd2be449c7eb