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BIOMD0000000552 - Ehrenstein2000 - Positive-Feedback model for the loss of acetylcholine in Alzheimer's disease

 

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Reference Publication
Publication ID: 10863547
Ehrenstein G, Galdzicki Z, Lange GD.
A positive-feedback model for the loss of acetylcholine in Alzheimer's disease.
Ann. N. Y. Acad. Sci. 2000; 899: 283-291
Biophysics Section, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA. gerry@helix.nih.gov  [more]
Model
Original Model: BIOMD0000000552.origin
Submitter: Audald Lloret i Villas
Submission ID: MODEL1410200001
Submission Date: 20 Oct 2014 13:31:24 UTC
Last Modification Date: 12 Dec 2014 15:03:14 UTC
Creation Date: 20 Oct 2014 14:37:13 UTC
Encoders:  Audald Lloret i Villas
set #1
bqbiol:hasVersion Human Disease Ontology Alzheimer's disease
set #2
bqbiol:hasTaxon Taxonomy Homo sapiens
set #3
bqbiol:isVersionOf Gene Ontology acetylcholine biosynthetic process
set #4
bqmodel:isDerivedFrom BioModels Database BIOMD0000000553
PubMed 9284295
Notes
Ehrenstein2000 - Positive-Feedback model for the loss of acetylcholine in Alzheimer's disease
Curated model derived from

BIOMD0000000553

This model is described in the article:

Ehrenstein G, Galdzicki Z, Lange GD.
Ann. N. Y. Acad. Sci. 2000; 899: 283-291

Abstract:

We describe a two-component positive-feedback system that could account for the large reduction of acetylcholine that is characteristic of patients with Alzheimer's disease (AD). One component is beta-amyloid-induced apoptosis of cholinergic cells, leading to a decrease in acetylcholine. The other component is an increase in the concentration of beta-amyloid in response to a decrease in acetylcholine. We describe each mechanism with a differential equation, and then solve the two equations numerically. The solution provides a description of the time course of the reduction of acetylcholine in AD patients that is consistent with epidemiological data. This model may also provide an explanation for the significant, but lesser, decrease of other neurotransmitters that is characteristic of AD.

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.

Model
Publication ID: 10863547 Submission Date: 20 Oct 2014 13:31:24 UTC Last Modification Date: 12 Dec 2014 15:03:14 UTC Creation Date: 20 Oct 2014 14:37:13 UTC
Mathematical expressions
Reactions
Loss of intracellular choline Abeta formation from APP Effect of extracellular ACh Decrease in the extracellular concentration of beta-amyloid
Rules
Assignment Rule (variable: aRel)      
Physical entities
Compartments Species
Brain a b aRel
Global parameters
k1 k2 k3 k4
Reactions (4)
 
 Loss of intracellular choline [a] → ;   {b} , {a} , {b}
 
 Abeta formation from APP  → [b];  
 
 Effect of extracellular ACh [b] → ;   {a} , {a}
 
 Decrease in the extracellular concentration of beta-amyloid [b] → ;   {b}
 
Rules (1)
 
 Assignment Rule (name: aRel) aRel = a/50
 
Functions (4)
 
 Constant flux (irreversible) lambda(v, v)
 
 Loss of intracellular choline lambda(k1, a, b, k1*a*b)
 
 Effect of extracellular ACh lambda(k3, a, k3*a)
 
 Decrease in the extracellular concentration of beta-amyloid lambda(k4, b, k4*b)
 
 Brain Spatial dimensions: 3.0  Compartment size: 1.0
 
 a
Compartment: Brain
Initial concentration: 50.0
 
 b
Compartment: Brain
Initial concentration: 0.0
 
  aRel
Compartment: Brain
Initial concentration: 1.0
 
Global Parameters (4)
 
 k1
Value: 0.007
Constant
 
 k2
Value: 0.33
Constant
 
 k3
Value: 0.0042
Constant
 
 k4
Value: 0.01
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000552

Curator's comment: (updated: 20 Oct 2014 15:06:26 GMT)

Figure 1 has been reproduced here. Time course of the decline in acetylcholine is plotted ranging different values for k2 parameter.

The simulation was done using Copasi v4.12 (Build 81) and the plots were generated using Gnuplot. The Copasi file of the model with simulation settings can be downloaded from the below link.

Additional file(s)
  • Ehrenstein2000 - Positive-Feedback model for the loss of acetylcholine in Alzheimer's disease:
    Copasi file of the model
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