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TODAY’S FOCUS: Researchers Close In on Mystery of Alzheimer’s Disease

October 22, 1985

DALLAS (AP) _ Researchers have identified a new kind of abnormality in the brains of people with Alzheimer’s disease that could be the best clue yet to the cause of the debilitating affliction.

The scientists found that the disease produces unusual changes in the fibers that serve as ″skeletons″ inside brain cells to help the cells hold their shape.

″No one believes these fibers are the cause of the disease,″ said Dr. Daniel Selkoe of Harvard Medical School, one of the scientists studying them. But they are an important step closer to the cause.

″These fibers we’re studying are the best available clue to what happens in Alzheimer’s disease,″ he said in an interview Sunday during the annual meeting in Dallas of the Society for Neuroscience.

Scientists have known for a long time that the brains of Alzheimer’s disease patients contain microscopic fibrous tangles and hardened deposits called plaques, but where these tangles and plaques came from was not known.

Selkoe and other researchers have now shown that the tangles and plaques contain some of the same proteins, or portions of the proteins, that are contained in the cytoskeletal fibers in normal brain cells, or neurons.

The finding adds to indications that the cause of Alzheimer’s may lie in the process controlling formation of the cytoskeletal structures.

Further, it allows scientists for the first time to begin using the powerful techniques of gene-splicing to fight Alzheimer’s.

Selkoe collaborators Ken Kosik, Rachel Neve and David Kurnit have already isolated the gene for one of the proteins found in both normal and abnormal neural fibers.

They can now use that gene to track Alzheimer’s disease in the unusual cases where it is inherited in families, Selkoe said.

With luck, genetic research could lead to the fundamental, underlying cause of all the changes seen in Alzheimer’s disease.

While in many cases family members of Alzheimer’s victims appear to have an unexplained predisposition to develop it, only rarely is the disease passed on like classic hereditary diseases, such as cystic fibrosis.

The reason for the variability could be that several genes may control the disease. These genes could interact in different ways in different individuals.

At present, there is no cure for Alzheimer’s, and nothing can be done even to alleviate its symptoms or to detect it early, before symptoms appear.

About 20 percent of the U.S. population will eventually get Alzheimer’s, and the number of cases is increasing as the population ages, said Dr. Clifford Saper of the University of Chicago during the neuroscience meeting. In about 35 years, one in four Americans will be over age 65, he said.

Care for Alzheimer’s victims now costs $20 billion a year, Saper said.

The disease, which causes at least 100,000 deaths a year, was first described in 1907 by Alois Alzheimer, a German psychiatrist. Alzheimer noted the symptoms: a progressive loss of memory and mental function and eventual inability to speak or perform even routine tasks.

Alzheimer was the first to note the tangles and plaques that occur in the brains of those with the illness. These hard, insoluble structures remain as tombstones marking the death of brain cells.

In the last 15 years, researchers have uncovered more.

Dr. Peter Davies of the Albert Einstein College of Medicine in New York was one of several scientists to find that only certain brain cells were affected.

Different brain cells use different chemicals, called neurotransmitters, to communicate. The researchers found that the disease primarily affected brain cells that used the neurotransmitter acetylcholine.

Dr. Donald Price of Johns Hopkins University in Baltimore and others reported that the damage seemed to occur in certain regions of the brain - near the base of the brain, for example, and in certain parts of the cortex, or outer layer of the brain.

Researchers have used various drugs to try to boost production of acetylcholine and thus restore the function of the neurons that require it, but the drugs have been unsuccessful, said Davies.

Some months ago, researchers at Dartmouth University in New Hampshire administered a drug directly into the skulls of patients, so it would go directly to the brain.

″It is impossible at this time to say whether anything happens,″ said Davies. Nevertheless, other groups are preparing to try the same strategy with different drugs, he said.

Selkoe and his colleagues believe that the tangles and plaques are important in Alzheimer’s disease because these abnormalities occur near neurons using acetylcholine, because they are more frequent in more severe cases of disease, and because they are found in the parts of the brain affected by the disease.

Selkoe’s group has shown that plaques and certain tangles called paired helical filaments share certain chemical properties. They have also shown that the plaques and tangles contain proteins that are not present in normal brains, or present only in extremely small quantities.

Other researchers have shown that the plaques and tangles also share some chemical properties with the cytoskeletons of normal neurons.

Growing evidence suggests that Alzheimer’s could be the result of some abnormal control of the process of manufacturing cytoskeleton components, said Price.The tangles could result from production of abnormal skeletal elements or overproduction of normal elements.

If that theory is correct, then the cause of Alzheimer’s disease could be found in that control system.

″A lot of movement has been made in the last year,″ said Selkoe. ″But it’s not what the public wants to hear.″ The cause of Alzheimer’s disease and its cure, he said, remain elusive.

-PX-10-22-85 0039EDT

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