Non Animal Testing Database

Mathematical model of amyloid beta dynamics in the presence of gamma-secretase inhibitors

November 2012
AstraZeneca, Macclesfield, United Kingdom
The mechanisms of amyloid-beta accumulation in Alzheimer's disease are still not well-known. One unanswered question is the rise of amyloid-beta levels after treatment with gamma secretase inhibitors in some cell lines. In this study, a mathematical model is proposed to quantitatively describe the dynamics of amyloid-beta in cell lines that undergo this phenomenon compared to those that do not. The results show that the changes in the dynamics of the amyloidogenic and non-amyloidogenic pathways are driven by the accumulation of C-terminal fragment 99 of the amyloid precursor protein. Also, the model is able to reproduce the amyloid-beta profiles of humans treated with gamma secretase inhibitors. Overall, this study proposes an effective mathematical model that can be used to develop new therapeutics that target amyloid-beta production in Alzheimer's disease.
Interplay between α-, β-, and γ-secretases determines biphasic amyloid-β protein level in the presence of a γ-secretase inhibitor
Claus Bendtsen
Added on: 08-08-2021
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