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research-article

A numerical study of sensitivity coefficients for a model of amyloid precursor protein and tau protein transport and agglomeration in neurons at the onset of Alzheimer's disease

[+] Author and Article Information
Ivan A. Kuznetsov

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Bioengineering, University of Pennsylvania, Philadelphia, PA 19104, USA
ivan.kuznetsov1@gmail.com

Andrey Kuznetsov

Dept. of Mechanical and Aerospace Engineering, North Carolina State University, Raleigh, NC 27695-7910, USA
avkuznet@ncsu.edu

1Corresponding author.

ASME doi:10.1115/1.4041905 History: Received June 22, 2018; Revised October 17, 2018

Abstract

Modeling of intracellular processes occurring during the development of Alzheimer's disease (AD) can be instrumental in understanding the disease and can potentially contribute to finding treatments for the disease. The model of intracellular processes in AD, which we previously developed, contains a large number of parameters. To distinguish between more important and less important parameters we performed a local sensitivity analysis of this model around the values of parameters that give the best fit with published experimental results. We show that the effect of model parameters on the total concentration of amyloid precursor protein (APP) and tau protein in the axon, respectively, is reciprocal to the effect of the same parameters on the average velocities of the same proteins during their transport in the axon. The results of our analysis also suggest that in the beginning of AD the aggregation of amyloid-ß and misfolded tau protein have little effect on transport of APP and tau in the axon, which suggests that early effects of AD may be reversible.

Copyright (c) 2018 by ASME
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