The Adaptive Immune System Restrains Alzheimer’s Disease (AD) Pathogenesis by Modulating Microglial Function
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE77574 | GEO | 2016/03/03
SECONDARY ACCESSION(S): PRJNA310838
REPOSITORIES: GEO
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Project description: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.
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2016-05-09 | MODEL1504240000 | BioModels