Abstract
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.
Highlights
Many neurodegenerative diseases are related to the propagation and accumulation of toxic proteins throughout the brain
We posit that the main reason for such reproducibility is that the overall progression of the disease is governed by generic transport processes and that the key difference between individual diseases, aside from the particular set of proteins involved, is the original location of the seeds, leading to a spatiotemporal evolution (Fig. 1) characteristic for (a,b) Alzheimer’s disease, (c) Parkinson’s disease, and (d) amyotrophic lateral sclerosis
(a) amyloid-β in Alzheimer’s disease (b) tau inclusions in Alzheimer’s disease (c) α−synuclein inclusions in Parkinson’s disease (d) TDP-43 inclusions in amyotrophic lateral sclerosis anisotropic transport process with a mechanical atrophy model to study the relative effects of seed location, anisotropy, and brain geometry on the toxic protein concentration and the resulting atrophy of brain tissue [12,13]
Summary
Many neurodegenerative diseases are related to the propagation and accumulation of toxic proteins throughout the brain. We posit that the main reason for such reproducibility is that the overall progression of the disease is governed by generic transport processes and that the key difference between individual diseases, aside from the particular set of proteins involved, is the original location of the seeds, leading to a spatiotemporal evolution (Fig. 1) characteristic for (a,b) Alzheimer’s disease, (c) Parkinson’s disease, and (d) amyotrophic lateral sclerosis.
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