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

ABSTRACT: Ehrenstein1997 - The choline-leakage hypothesis in Alzheimer's disease This model is described in the article: The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's disease. 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. This model is hosted on BioModels Database and identified by: BIOMD0000000553. 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: BIOMD0000000553 | BioModels | 2024-09-02

REPOSITORIES: BioModels

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			Action	DRS
	BIOMD0000000553?filename=BIOMD0000000553-biopax2.owl	Owl
	BIOMD0000000553?filename=BIOMD0000000553-biopax3.owl	Owl
	BIOMD0000000553?filename=BIOMD0000000553-matlab.m	Other
	BIOMD0000000553?filename=BIOMD0000000553-octave.m	Other
	BIOMD0000000553?filename=BIOMD0000000553.m	Other

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Publications

The choline-leakage hypothesis for the loss of acetylcholine in Alzheimer's disease.

Ehrenstein G G Galdzicki Z Z Lange G D GD

Biophysical journal 19970901 3

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 ...[more]

PMID: 9284295

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