title: Lipid Raft Size and Lipid Mobility in Non-raft Domains Increase during Aging and Are Exacerbated in APP/PS1 Mice Model of Alzheimer's Disease. Predictions from an Agent-Based Mathematical Model.
abstract: A connection between lipid rafts and Alzheimer's disease has been studied during the last decades. Mathematical modeling approaches have recently been used to correlate the effects of lipid composition changes in the physicochemical properties of raft-like membranes. Here we propose an agent based model to assess the effect of lipid changes in lipid rafts on the evolution and progression of Alzheimer's disease using lipid profile data obtained in an established model of familial Alzheimer's disease. We have observed that lipid raft size and lipid mobility in non-raft domains are two main factors that increase during age and are accelerated in the transgenic Alzheimer's disease mouse model. The consequences of these changes are discussed in the context of neurotoxic amyloid β production. Our agent based model predicts that increasing sterols (mainly cholesterol) and long-chain polyunsaturated fatty acids (LCPUFA) (mainly DHA, docosahexaenoic acid) proportions in the membrane composition might delay the onset and progression of the disease.
authors.affiliation: Systems Biology and Mathematical Modelling Group, Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Instituto de Tecnologías Biomédicas, CIBICAN, Universidad de La Laguna San Cristóbal de La Laguna, Spain.
authors.forename: Guido
authors.initials: G
authors.lastname: Santos
authors.affiliation: Laboratorio de Fisiología y Biofísica de Membranas, Departamento de Biología Animal y Edafología y Geología, Facultad de Ciencias, Unidad Asociada de Investigación ULL-CSIC, Universidad de La Laguna San Cristóbal de La Laguna, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Díaz
authors.affiliation: Systems Biology and Mathematical Modelling Group, Departamento de Bioquímica, Microbiología, Biología Celular y Genética, Instituto de Tecnologías Biomédicas, CIBICAN, Universidad de La Laguna San Cristóbal de La Laguna, Spain.
authors.forename: Néstor V
authors.initials: NV
authors.lastname: Torres
keywords: Alzheimer's disease; DHA; agent based model; cholesterol; lipid composition; lipid rafts; mathematical modeling; membrane domains