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

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.

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