title: Early Treatment Critical: Bexarotene Reduces Amyloid-Beta Burden In Silico.
abstract: Amyloid-beta peptides have long been implicated in the pathology of Alzheimer's disease. Bexarotene, a drug approved by the U.S. Food and Drug Administration for treating a class of non-Hodgkin's lymphoma, has been reported to facilitate the removal of amyloid-beta. We have developed a mathematical model to explore the efficacy of bexarotene treatment in reducing amyloid-beta load, and simulate amyloid-beta production throughout the lifespan of diseased mice. Both aspects of the model are based on and consistent with previous experimental results. Beyond what is known empirically, our model shows that low dosages of bexarotene are unable to reverse symptoms in diseased mice, but dosages at and above an age-dependent critical concentration can recover healthy brain cells. Further, early treatment was shown to have significantly improved efficacy versus treatment in older mice. Relevance with respect to bexarotene-based amyloid-beta-clearance mechanism and direct treatment for Alzheimer's disease is emphasized.
authors.affiliation: Department of Mathematical Sciences, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
authors.forename: Joseph
authors.identifier: http://orcid.org/0000-0001-8500-4032
authors.initials: J
authors.lastname: Rosenthal
authors.affiliation: Howard P. Isermann Department of Chemical and Biological Engineering and Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
authors.forename: Georges
authors.initials: G
authors.lastname: Belfort
authors.affiliation: Department of Mathematical Sciences, Rensselaer Polytechnic Institute, Troy, New York, United States of America.
authors.forename: David
authors.initials: D
authors.lastname: Isaacson
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000077610:Bexarotene; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D003198:Computer Simulation; D004195:Disease Models, Animal; D051379:Mice; D008962:Models, Theoretical; D013764:Tetrahydronaphthalenes / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D016588:Anticarcinogenic Agents; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene