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 influence of model parameters on the total concentrations of amyloid precursor protein (APP) and tubulin-associated unit (tau) protein in the axon is reciprocal to the influence 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-β and misfolded tau protein have little effect on transport of APP and tau in the axon, which suggests that early damage in AD may be reversible.
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March 2019
Research-Article
A Numerical Study of Sensitivity Coefficients for a Model of Amyloid Precursor Protein and Tubulin-Associated Unit Protein Transport and Agglomeration in Neurons at the Onset of Alzheimer's Disease
I. A. Kuznetsov,
I. A. Kuznetsov
Perelman School of Medicine,
University of Pennsylvania,
Philadelphia, PA 19104;
University of Pennsylvania,
Philadelphia, PA 19104;
Department of Bioengineering,
University of Pennsylvania,
Philadelphia, PA 19104
e-mail: ivan.kuznetsov@uphs.upenn.edu
University of Pennsylvania,
Philadelphia, PA 19104
e-mail: ivan.kuznetsov@uphs.upenn.edu
Search for other works by this author on:
A. V. Kuznetsov
A. V. Kuznetsov
Department of Mechanical and
Aerospace Engineering,
North Carolina State University,
Raleigh, NC 27695-7910
e-mail: avkuznet@ncsu.edu
Aerospace Engineering,
North Carolina State University,
Raleigh, NC 27695-7910
e-mail: avkuznet@ncsu.edu
Search for other works by this author on:
I. A. Kuznetsov
Perelman School of Medicine,
University of Pennsylvania,
Philadelphia, PA 19104;
University of Pennsylvania,
Philadelphia, PA 19104;
Department of Bioengineering,
University of Pennsylvania,
Philadelphia, PA 19104
e-mail: ivan.kuznetsov@uphs.upenn.edu
University of Pennsylvania,
Philadelphia, PA 19104
e-mail: ivan.kuznetsov@uphs.upenn.edu
A. V. Kuznetsov
Department of Mechanical and
Aerospace Engineering,
North Carolina State University,
Raleigh, NC 27695-7910
e-mail: avkuznet@ncsu.edu
Aerospace Engineering,
North Carolina State University,
Raleigh, NC 27695-7910
e-mail: avkuznet@ncsu.edu
Manuscript received June 22, 2018; final manuscript received October 17, 2018; published online January 18, 2019. Assoc. Editor: Jeffrey Ruberti.
J Biomech Eng. Mar 2019, 141(3): 031006 (9 pages)
Published Online: January 18, 2019
Article history
Received:
June 22, 2018
Revised:
October 17, 2018
Citation
Kuznetsov, I. A., and Kuznetsov, A. V. (January 18, 2019). "A Numerical Study of Sensitivity Coefficients for a Model of Amyloid Precursor Protein and Tubulin-Associated Unit Protein Transport and Agglomeration in Neurons at the Onset of Alzheimer's Disease." ASME. J Biomech Eng. March 2019; 141(3): 031006. https://doi.org/10.1115/1.4041905
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