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. 2018 Oct 8;7(11):759–770. doi: 10.1002/psp4.12351

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© 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.

This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

PMC Copyright notice

Quantitative systems pharmacology model for lipid dysregulation in Alzheimer disease and pharmacological interventions. Relevant physiology is captured assuming three compartments: plasma, cerebrospinal fluid (CSF), and the brain. Reactants associated with cholesterol and sphingolipid metabolism, amyloid precursor protein (APP) processing/metabolism and sphingosine‐1‐phosphate receptor 5 (S1PR5) binding are described in the brain. They interact and/or distribute between the compartments according to their properties. Pharmacological interventions are implemented using empirical models for pharmacokinetic (PK) and pharmacological effect, as described in the text.