Kyrtsos2011 - A systems biology model for Alzheimer's disease (Cholesterol in AD)

ABSTRACT: Kyrtsos2011 - A systems biology model for Alzheimer's disease (Cholesterol in AD) Encoded non-curated model. Issues: - Confusing HmgCoA differential equation - Confusing d2 and t1 parameters - Lack of initial values for several key species This model is described in the article: Of Mice and Math: A Systems Biology Model for Alzheimer's disease Kyrtsos, Christina Rose UMD Theses and Dissertations Abstract: Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder in the US, affecting over 1 in 8 people over the age of 65. There are several well-known pathological changes in the brains of AD patients, namely: the presence of diffuse beta amyloid plaques derived from the amyloid precursor protein (APP), hyper-phosphorylated tau protein, neuroinflammation and mitochondrial dysfunction. Recent studies have shown that cholesterol levels in both the plasma and the brain may play a role in disease pathogenesis, however, this exact role is not well understood. Additional proteins of interest have also been identified (ApoE, LRP-1, IL-1) as possible contributors to AD pathogenesis. To help understand these roles better, a systems biology mathematical model was developed. Basic principles from graph theory and control analysis were used to study the effect of altered cholesterol, ApoE, LRP and APP on the system as a whole. Negative feedback regulation and the rate of cholesterol transfer between astrocytes and neurons were identified as key modulators in the level of beta amyloid. Experiments were run concurrently to test whether decreasing plasma and brain cholesterol levels with simvastatin altered the expression levels of beta amyloid, ApoE, and LRP-1, to ascertain the edge directions in the network model and to better understand whether statin treatment served as a viable treatment option for AD patients. The work completed herein represents the first attempt to create a systems-level mathematical model to study AD that looks at intercellular interactions, as well as interactions between metabolic and inflammatory pathways. This model is hosted on BioModels Database and identified by: MODEL1504240000. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

DISEASE(S): Alzheimer's Disease

SUBMITTER: Audald Lloret i Villas  

PROVIDER: MODEL1504240000 | BioModels | 2016-05-09

REPOSITORIES: BioModels