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Researchers at McLean Hospital, MIT make finding related to Alzheimer's

CAMBRIDGE, Mass.--Researchers at McLean Hospital and the Massachusetts Institute of Technology's Clinical Research Center (CRC), using a new assay technique, have obtained data showing that the brain's ability to take up a key nutrient from the blood decreases sharply with age.

The results, anticipated from the findings of earlier pilot studies, suggests an explanation for why even those with a genetic predisposition to Alzheimer's disease don't develop symptoms until they age.

The investigation of the nutrient choline was published in the September 20 issue of the Journal of the American Medical Association (JAMA). Choline, vital to brain function, is obtained almost entirely from the diet.

The work was partially supported by a one-year research grant administered by the CRC using MIT patent royalties and by a research grant from the National Institute of Mental Health and an NIH grant to the CRC.

The study was based on continuing investigations in the laboratory of MIT Professor Richard J. Wurtman, MD, PhD., one of the authors of the JAMA paper. He is director of the CRC and a member of the Department of Brain and Cognitive Science. Professor Wurtman's investigations were the first to show that brain levels of choline could influence the ability of nerve cells to make the neurotransmitter acetylcholine, and the ability of all cells to make phosphatidylcholine (lecithin), a key constituent of all membranes. Dr. Wurtman's earlier work also showed that when choline is in short supply, its use for these two pathways is competitive.

"When the nerve cells become active," he said, "almost all of the choline is shunted into making acetylcholine, and almost none into making membranes. So the amount of membrane in each cell disappears--by a process termed 'autocannibalism.'

"Presumably, the reduction in the uptake of blood choline into brains of aged individuals (which the current study documents) would promote this 'autocannibalism' and lead to damage to, or even the death of, nerve cells in the brain."

The lead author on the JAMA study was Bruce M. Cohen, MD, PhD., of McLean's Brain Imaging Center, Harvard Medical School's Department of Psychiatry and the MIT Clinical Research Center (CRC). Other authors were Perry F. Renshaw, MD, PhD; Andrew L. Stoll, MD; Deborah Yurgelun-Todd, PhD; and Suzann M. Babb, all of McLean Hospital. Dr. Renshaw and Dr. Stoll also have CRC appointments.

Twenty-eight volunteers took part in the study, 12 of them between the ages of 20 and 40 and 16 between the ages of 60 and 85. After an overnight fast, they received the equivalent of 4 grams of a choline salt.

Using a new, noninvasive assay technique (Magnetic Resonance Spectroscopy), blood and brain levels were measured periodically.

"We found that blood choline levels rose to comparable extents in young and old people," Professor Wurtman said. "However, brain levels showed a much smaller rise in the older subjects.

"These observations suggest that normal choline intake in a younger person might not be optimal once one ages. They also provide one hypothesis for explaining why Alzheimer's Disease tends to be a disease of the aged even though the genes that can cause it in many patients are, in fact, present from birth."

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