Alzheimer's memory loss link reported Protein treatment may help, say researchers

July 16, 1993|By Los Angeles Times

Researchers at the University of California, Los Angeles, have discovered what they believe to be the mechanism of memory loss in Alzheimer's and other neurodegenerative diseases. The finding potentially opens the door to the development of new drugs that can halt memory deterioration in such disorders.

The discovery, reported today in the journal Science, may also lead to a new understanding of the growth and death of cells during the development of the brain early in life.

Dr. Dale E. Bredesen, a UCLA gerontologist, and his colleagues have found that a protein on the surface of key memory cells kills the cells unless a brain hormone called nerve growth factor, or NGF, is bound to, or locked onto, that protein. He also found that the protein, an NGF receptor called p75, "is in the exact same cells that are the most severely affected and earliest to die in Alzheimer's disease," he said. "That is unlikely to be a coincidence."

This discovery suggests that the death of brain cells in Alzheimer's is directly caused by the p75 receptor. It also indicates that memory loss in diseases of aging could be minimized by treating brain cells with NGF or with drugs that mimic the action of NGF by binding to the protein and preventing its killing effects.

"This has profound implications for therapy of Alzheimer's" and related diseases, said neurobiologist Eric Shooter of Stanford University. "There are sure to be clinical trials as soon as somebody figures out how to get [NGF] into the brain."

To find out what the receptor does, Dr. Bredesen's team coaxed brain cells containing it to grow in test tubes. They discovered that the cells would grow and thrive as long as NGF was present. But when NGF was removed from the test tubes, the cells unexpectedly died. Cells that did not have the receptor remained alive.

"This is the first time a receptor, in and of itself, has been shown to demonstrate this ability" to kill cells, Dr. Bredesen said. "Growth factor receptors have generally been thought of to have positive effects when they bind with a substance like nerve growth factor, and as being innocuous when they are not bound . . . Nobody thought it would play an active role in the death of cells."

The results suggest that, if given early during the course of Alzheimer's, NGF could block the mental deterioration caused by the disease.

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