Ehrenstein1997 - The choline-leakage hypothesis in Alzheimer's disease

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Ehrenstein1997 - The choline-leakage hypothesis in Alzheimer's disease

This model is described in the article:

Ehrenstein G, Galdzicki Z, Lange GD.
Biophys. J. 1997 Sep; 73(3): 1276-1280

Abstract:

We present a hypothesis for the loss of acetylcholine in Alzheimer's disease that is based on two recent experimental results: that beta-amyloid causes leakage of choline across cell membranes and that decreased production of acetylcholine increases the production of beta-amyloid. According to the hypothesis, an increase in beta-amyloid concentration caused by proteolysis of the amyloid precursor protein results in an increase in the leakage of choline out of cells. This leads to a reduction in intracellular choline concentration and hence a reduction in acetylcholine production. The reduction in acetylcholine production, in turn, causes an increase in the concentration of beta-amyloid. The resultant positive feedback between decreased acetylcholine and increased beta-amyloid accelerates the loss of acetylcholine. We compare the predictions of the choline-leakage hypothesis with a number of experimental observations. We also approximate it with a pair of ordinary differential equations. The solutions of these equations indicate that the loss of acetylcholine is very sensitive to the initial rate of beta-amyloid production.

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Format
SBML (L2V4)
Related Publication
  • The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's disease.
  • Ehrenstein G, Galdzicki Z, Lange GD
  • Biophysical Journal , 9/ 1997 , Volume 73 , pages: 1276-1280
  • Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. gerry@helix.nih.gov
  • We present a hypothesis for the loss of acetylcholine in Alzheimer's disease that is based on two recent experimental results: that beta-amyloid causes leakage of choline across cell membranes and that decreased production of acetylcholine increases the production of beta-amyloid. According to the hypothesis, an increase in beta-amyloid concentration caused by proteolysis of the amyloid precursor protein results in an increase in the leakage of choline out of cells. This leads to a reduction in intracellular choline concentration and hence a reduction in acetylcholine production. The reduction in acetylcholine production, in turn, causes an increase in the concentration of beta-amyloid. The resultant positive feedback between decreased acetylcholine and increased beta-amyloid accelerates the loss of acetylcholine. We compare the predictions of the choline-leakage hypothesis with a number of experimental observations. We also approximate it with a pair of ordinary differential equations. The solutions of these equations indicate that the loss of acetylcholine is very sensitive to the initial rate of beta-amyloid production.
Contributors
Audald Lloret i Villas

Metadata information

is
BioModels Database MODEL1410200000
BioModels Database BIOMD0000000553
isDescribedBy
PubMed 9284295
hasTaxon
Taxonomy Homo sapiens
isVersionOf
hasVersion
Human Disease Ontology Alzheimer's disease
Curation status
Curated
  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: 20-Oct-2014 13:23:02
  • Last Modified: 17-Mar-2015 17:01:06
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 17-Mar-2015 17:01:06
    • Submitted by: Audald Lloret i Villas
    • With comment: Current version of Ehrenstein1997 - The choline-leakage hypothesis in Alzheimer's disease
  • Version: 1 public model Download this version
    • Submitted on: 20-Oct-2014 13:23:02
    • Submitted by: Audald Lloret i Villas
    • With comment: Original import of Ehrenstein1997 - The choline-leakage hypothesis in Alzheimer's disease
Curator's comment:
(added: 20 Oct 2014, 16:21:26, updated: 20 Oct 2014, 16:21:26)
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.