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Brain geometry matters in Alzheimer disease progression: a simulation study

Hoore, M.; Kelling, J.; Sayadmanesh, M.; Mitra, T.; Schips, M.; Meyer-Hermann, M.

The Amyloid cascade hypothesis (ACH) for Alzheimer's disease (AD) is modeled over the whole brain tissue with a set of partial differential equations. Our results show that the amyloid plaque formation is critically dependent on the secretion rate of amyloid β(Aβ), which is proportional to the product of neural density and neural activity. Neural atrophy is similarly related to the secretion rate of Aβ. Due to a heterogeneous distribution of neural density and brain activity throughout the brain, amyloid plaque formation and neural death occurs heterogeneously in the brain. The geometry of the brain and microglia migration in the parenchyma bring more complexity into the system and result in a diverse amyloidosis and dementia pattern of different brain regions. Although the pattern of amyloidosis in the brain cortex from in-silico results is similar to experimental autopsy findings, they mismatch at the central regions of the brain, suggesting that ACH is not able to explain the whole course of AD without considering other factors, such as tau-protein aggregation or neuroinflammation.

Keywords: Neurdegenerative disease; Alzheimer's disease; Amyloid cascade hypothesis; mult-phase model

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Permalink: https://www.hzdr.de/publications/Publ-31371
Publ.-Id: 31371