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Hypothesis for cause of memory loss in Alzheimer's disease proposed



Mayo 23, 1994

NIA Press Office | 301-496-1752 | nianews3@mail.nih.gov



An unexpected discovery by researchers at The National Institutes of Health (NIH), may help to explain how Alzheimer's disease causes memory loss. The research shows that beta amyloid, a common protein in the brain, can make cell membranes leak choline, and thus reduce production of acetylcholine in cells. Choline, an essential ingredient in acetylcholine, has been known for many years to help store and retrieve memories. Two hallmarks of Alzheimer's disease are accumulation in the brain of beta amyloid and reduction of the concentration of acetylcholine. In Alzheimer's disease, as well as in older subjects with Down syndrome, the brain cells which produce acetylcholine are known to die.

The research is reported in the May 23rd issue of Brain Research by investigators at the National Institute on Aging (NIA) and the National Institute of Neurological Disorders (NINDS). According to Dr. Stanley Rapoport, Chief of the NIA's Laboratory of Neurosciences, "We think that increased leakage of choline through the nerve cell membranes, due to prolonged exposure to excess concentrations of beta amyloid, may make these cells more vulnerable. This could contribute to the symptoms of Alzheimer's disease and Down's syndrome dementia."

Dr. Rapoport and his colleagues performed experiments on cells cultured in laboratory dishes. They added increasing amounts of beta amyloid to the cells, and used fine glass tubing and electrical recordings to examine leakiness (permeability) of the cell membranes in the presence or absence of choline. The more beta amyloid they added, the greater the leakiness in the presence of choline; in the absence of choline, leakiness did not occur. Their results provide evidence for a mechanism of a membrane carrier for choline leakage.

"There still are several difficulties in trying to relate these findings in a culture dish to what may happen in brains of patients with Alzheimer's," Rapoport says. "It is not yet known how much beta amyloid can be present in the brain without any damage being done, nor do we know the effect of prolonged exposure to beta amyloid, compared to the short periods of exposure (24 hours) in our experimental studies. However, we now have a hypothesis to explain some observed nerve cell loss in Alzheimer's disease.

Working with Dr. Rapoport are Dr. Zygmunt Galdzicki, first author of the manuscript, Drs. Ryuichi Fukuyama and Kishena C. Wadhwani of the Laboratory of Neurosciences, NIA, and as part of the collaborative effort, Dr. Gerald Ehrenstein of the Clinical Neurology Branch, NINDS, at the NIH.

The NIA, a component of NIH, is the lead federal agency supporting and conducting Alzheimer's disease research, including studies of the basic, clinical, and epidemiological aspects of this and other related dementias of aging.

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