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

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Short description
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

Curation status
Curated
  • Model originally submitted by : Audald Lloret i Villas
  • Submitted: Oct 20, 2014 1:23:02 PM
  • Last Modified: Mar 17, 2015 5:01:06 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Mar 17, 2015 5:01:06 PM
    • 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: Oct 20, 2014 1:23:02 PM
    • 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.