The paper presents a conceptual mathematical model for Alzheimer's disease (AD). According to the so-called amyloid cascade hypothesis, we assume that the progression of AD is associated with the presence of soluble toxic oligomers of beta-amyloid. Monomers of this protein are produced normally throughout life, but a change in the metabolism may increase their total production and, through aggregation, ultimately results in a large quantity of highly toxic polymers. The evolution from monomeric amyloid produced by the neurons to senile plaques (long and insoluble polymeric amyloid chains) is modelled by a system of ordinary differential equations (ODEs), in the spirit of the Smoluchowski equation. The basic assumptions of the model are that, at the scale of suitably small representative elementary volumes (REVs) of the brain, the production of monomers depends on the average degradation of the neurons and in turn, at a much slower timescale, the degradation is caused by the number of toxic oligomers. To mimic prion-like diffusion of the disease in the brain, we introduce an interaction among adjacent REVs that can be assumed to be isotropic or to follow given preferential patterns. We display the results of numerical simulations which are obtained under some simplifying assumptions. For instance, the amyloid cascade is modelled by just three ordinary differential equations (ODEs), and the simulations refer to abstract 2D domains, simplifications which can be easily avoided at the price of some additional computational costs. Since the model is suitably flexible to incorporate other mechanisms and geometries, we believe that it can be generalised to describe more realistic situations.

Bertsch, M., Franchi, B., Meacci, L., Primicerio, M., Tesi, M.c. (2021). The amyloid cascade hypothesis and Alzheimer's disease: a mathematical model. EUROPEAN JOURNAL OF APPLIED MATHEMATICS, 32(5), 749-768 [10.1017/S0956792520000339].

The amyloid cascade hypothesis and Alzheimer's disease: a mathematical model

Bertsch M.;
2021

Abstract

The paper presents a conceptual mathematical model for Alzheimer's disease (AD). According to the so-called amyloid cascade hypothesis, we assume that the progression of AD is associated with the presence of soluble toxic oligomers of beta-amyloid. Monomers of this protein are produced normally throughout life, but a change in the metabolism may increase their total production and, through aggregation, ultimately results in a large quantity of highly toxic polymers. The evolution from monomeric amyloid produced by the neurons to senile plaques (long and insoluble polymeric amyloid chains) is modelled by a system of ordinary differential equations (ODEs), in the spirit of the Smoluchowski equation. The basic assumptions of the model are that, at the scale of suitably small representative elementary volumes (REVs) of the brain, the production of monomers depends on the average degradation of the neurons and in turn, at a much slower timescale, the degradation is caused by the number of toxic oligomers. To mimic prion-like diffusion of the disease in the brain, we introduce an interaction among adjacent REVs that can be assumed to be isotropic or to follow given preferential patterns. We display the results of numerical simulations which are obtained under some simplifying assumptions. For instance, the amyloid cascade is modelled by just three ordinary differential equations (ODEs), and the simulations refer to abstract 2D domains, simplifications which can be easily avoided at the price of some additional computational costs. Since the model is suitably flexible to incorporate other mechanisms and geometries, we believe that it can be generalised to describe more realistic situations.
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore MAT/05
English
Con Impact Factor ISI
amyloid cascade hypothesis
mathematical models of Alzheimer's disease
Smoluchowski equations
Bertsch, M., Franchi, B., Meacci, L., Primicerio, M., Tesi, M.c. (2021). The amyloid cascade hypothesis and Alzheimer's disease: a mathematical model. EUROPEAN JOURNAL OF APPLIED MATHEMATICS, 32(5), 749-768 [10.1017/S0956792520000339].
Bertsch, M; Franchi, B; Meacci, L; Primicerio, M; Tesi, Mc
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/304335
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