A continuous-time mathematical model and discrete approximations for the aggregation of β-Amyloid.

Abstract:

:Alzheimer's disease is a degenerative disorder characterized by the loss of synapses and neurons from the brain, as well as the accumulation of amyloid-based neuritic plaques. While it remains a matter of contention whether β-amyloid causes the neurodegeneration, β-amyloid aggregation is associated with the disease progression. Therefore, gaining a clearer understanding of this aggregation may help to better understand the disease. We develop a continuous-time model for β-amyloid aggregation using concepts from chemical kinetics and population dynamics. We show the model conserves mass and establish conditions for the existence and stability of equilibria. We also develop two discrete-time approximations to the model that are dynamically consistent. We show numerically that the continuous-time model produces sigmoidal growth, while the discrete-time approximations may exhibit oscillatory dynamics. Finally, sensitivity analysis reveals that aggregate concentration is most sensitive to parameters involved in monomer production and nucleation, suggesting the need for good estimates of such parameters.

journal_name

J Biol Dyn

authors

Ackleh AS,Elaydi S,Livadiotis G,Veprauskas A

doi

10.1080/17513758.2020.1869843

keywords:

[" β-Amyloid","92C45","Alzheimer's disease","aggregation","neurodegenerative diseases","nonstandard discretization schemes"]

subject

Has Abstract

pub_date

2021-12-01 00:00:00

pages

109-136

issue

1

eissn

1751-3758

issn

1751-3766

journal_volume

15

pub_type

杂志文章

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