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Associated Press

Experiment In Mice May Lead To Early Test For Alzheimer's Disease, Researchers Say
March 21, 2002

WASHINGTON (AP) - Measuring the levels of a plaque-forming protein in the blood may identify Alzheimer's disease changes in the brain before other symptoms appear, according to researchers who tested the technique on mice.

Experiments at Washington University School of Medicine in St. Louis found that injecting an antibody into mice caused a sudden flood in the blood stream of amyloid-beta, a protein that forms neuron-destroying plaques in the brain.

Now a new study, using mice, shows that the level of amyloid-beta in the blood after the antibody injection is an indication of the amount of plaques forming in the brain, said David M. Holtzman, a Washington University neurologist and Alzheimer's disease researcher. He is a co-author of the study appearing Friday in the journal Science.

"We show in this study that the amount of amyloid-beta that comes out of the brain and into the blood stream is a very good reflection in these animals of how much is deposited in these plaques," said Holtzman.

He emphasized that although the technique works in a strain of mice that develop Alzheimer's, it is still not known if the test would work in humans. Because the disease progresses so slowly, Holtzman said it would take at least five years of studies before the test could be proven in human patients.

Holtzman said the study is a part of a major effort by Alzheimer's disease researchers to find a way to identify people who will develop the disease before they have obvious symptoms.

Right now, Alzheimer's can only be definitely proven at autopsy, although some clinical tests can diagnose the disease to a high degree of accuracy after profound symptoms have appeared.

"One of the hottest thing now (among researchers) is to figure out a diagnostic tool for Alzheimer's," said Holtzman.

There currently are no proven and effective drugs to cure or control the progression of Alzheimer's, although there are several candidates being tested. Some studies have suggested that folic acid and cholesterol control drugs can be beneficial, but research is still under way. Holtzman said that an early diagnostic test would enable doctors to identify patients who need treatment, allow tracking of the disease progression and help to test candidate drugs.

There are an estimated 4 million Americans with Alzheimer's disease now, but the total is expected to grow to about 14 million by the year 2050.

Amyloid-beta is a normal substance in the body, but starting at about age 50 it can accumulate in plaques in the brain. These plaques are linked to the death of neurons, causing a gradual loss of memory, control of body function and leading eventually to death.

"By the time a patient has the earliest clinical symptoms of Alzheimer's, there already is a massive amount of amyloid in the brain," said Holtzman. "It is a very slow process over 10 to 20 years."

He said the study in mice suggests that the blood test could identify the tendency to form amyloid-beta plaques at a very early point in the disease.

Bill Thies, vice president for medical and scientific affairs of the Alzheimer's Association, said a blood test to diagnose Alzheimer's would be an important advance in the battle against the disease.

"We really do need a biological way to track the disease," he said. "If we had that, it would increase our ability to identify people and would greatly accelerate clinical trials" of candidate Alzheimer's drugs.

However, he noted that whether or not the Washington University technique could become such a test for humans "is still an open question."

"A lot of work needs to be done before this technique could be established as a diagnostic," said Thies.

Copyright 2002 The Associated Press. All rights reserved.

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