Biophysical Journal 73: 1276-1280 (1997)
© 1997 the Biophysical Society

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

Biophysics Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA. gerry@helix.nih.gov

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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				G. EHRENSTEIN, Z. GALDZICKI, and G. D. LANGE A Positive-Feedback Model for the Loss of Acetylcholine in Alzheimer's Disease Ann. N.Y. Acad. Sci., January 1, 2000; 899(1): 283 - 291. [Abstract] [Full Text] [PDF]