THE VIRGINIAN-PILOT
Copyright (c) 1996, Landmark Communications, Inc.
DATE: Friday, October 4, 1996 TAG: 9610040529
SECTION: FRONT PAGE: A1 EDITION: FINAL
SOURCE: BY PAUL RECER, ASSOCIATED PRESS
DATELINE: WASHINGTON LENGTH: 74 lines
A new laboratory-engineered mouse suffers the same decline from Alzheimer's disease as do humans: lost memory and wasted brain cells. The mouse will give researchers a more accurate way to test drugs against the disorder.
The Alzheimer's Association called the mouse ``an important new research tool,'' and a National Institutes of Health expert said the mouse is ``good news for patients with Alzheimer's disease.''
A University of Minnesota team led by Dr. Karen Hsiao developed the rodent by inserting into a mouse embryo the mutated gene linked to Alzheimer's brain cell damage in humans.
Experiments testing the animals' thinking ability show that the new mouse breed suffers from a loss of memory that mimics the decline seen in humans, Hsiao said. The mouse brain also develops beta amyloid plaques, a substance found in the brains of Alzheimer's patients.
``This is the first time that anybody has made a mouse that shows an association between plaques and a functional loss of learning memory which is very much like Alzheimer's disease,'' Hsiao said.
A report on the mouse study is being published today in Science, the journal of the American Association for the Advancement of Science.
Dr. Thomas Chase, an Alzheimer's disease expert at the National Institutes of Health, said developing the lab mouse ``will enable the testing of drugs that get at the basic disease process.''
Drugs now available, he said, appear to treat only Alzheimer's symptoms.
Zaven Khachaturian, a scientist who heads the Alzheimer's Association Ronald and Nancy Reagan Research Institute, said the most important element of the new mouse is that it ``shows the behavioral deficits that are comparable to what is happening in humans.''
He said mice developed in other labs have Alzheimer's brain lesions like those in humans but exhibit none of the changes in memory and learning ability that Hsiao demonstrates with the new mouse.
``Caregivers want their loved ones to retain their functional abilities as long as possible,'' Khachaturian said. ``This mouse model should help us find those therapies.''
The Minnesota researchers ``made'' the mouse by putting into a mouse egg the human gene that manufactures the compound amyloid precursor protein. This substance helps form beta amyloid deposits in the brains of Alzheimer's disease patients.
The mouse was mated with a normal mouse, Hsiao said, and half the offspring had the Alzheimer's gene.
Mouse behavior was tested by putting the animals into a 3-foot-square pool of water surrounded by bright colors and patterns. Inside the pool is a platform refuge.
In training sessions, the mice learn to find the platform by lining it up with the bright background patterns. Normal mice memorize this location and quickly find it in later tests. Mice used in the testing were all litter-mates but only about half had the Alzheimer's gene.
When tested at a young age, Hsiao said, the mice with the Alzheimer's gene performed as well as control mice, which have normal genes. But as the animals aged, the Alzheimer's-carrying mice showed a loss of thinking ability.
``We can't tell any significant difference at three months or at six months,'' Hsiao said. But at nine months, she said, the Alzheimer's mouse ``couldn't learn or couldn't remember where the platform was. . . . When the mice got older, they swam aimlessly.''
She said this parallels the experience seen in Alzheimer's disease. Most patients develop the brain disorder in their 60s. The disease wipes out memory and eventually destroys all brain function, causing death.
Hsiao said the mice also were tested in a dry escape maze. The animals were placed in a box with three separate pathways, only one of which offered an escape. Mice normally would test the paths, one after the other, until the way out was found.
The older Alzheimer's mice, however, ``forget to explore all three exits. . ILLUSTRATION: Color photo
The mouse was ``made'' by inserting a human gene into it. by CNB