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Scientists Make Mice With Alzheimer-Like Disease

December 12, 1991

NEW YORK (AP) _ A fragment of a human gene made mice develop brain abnormalities like those seen in Alzheimer’s patients, making the animals useful for studying the human disorder, researchers reported today.

″We have in the mouse brain what one would expect to see if mice got Alzheimer’s disease,″ said Dr. Jon Gordon, a professor of geriatrics and adult development at the Mount Sinai School of Medicine in New York.

The abnormalities included protein-bearing deposits called plaques, nerve cell features called neurofibrillary tangles and brain cell degeneration.

The mice also showed abnormal behavior, Gordon said.

The animals should be useful in developing better ways to diagnose Alzheimer’s disease in humans and in testing potential therapies, he said. A firm diagnosis of Alzheimer’s generally is made by examining brain tissue after death.

Gordon presents the work in today’s issue of the journal Nature with Gerald Higgins of the National Institute on Aging and Shigeki Kawabata of Yamanouchi Pharmaceutical Co. Ltd. in Tokyo.

″I think this is very exciting work, and I think it’s a real step forward in research related to Alzheimer’s disease,″ said Dr. Donald Price of the Johns Hopkins Medical Institutions in Baltimore.

The mice provide ″the most useful animal model yet for the disease,″ Harvard researcher Dr. Dennis Selkoe wrote in a Nature editorial. The animals show more Alzheimer-like brain changes than did mice reported earlier this year, he said.

An estimated 4 million Americans, including about 10 percent of the population older than 65, have Alzheimer’s disease, according to the Alzheimer’s Association. It is a progressive brain condition that attacks memory, thinking and behavior. No cause or cure is known.

Researchers created the mice by injecting embryos with about 2,000 copies apiece of a fragment of a human gene. The full gene lets the body create amyloid precursor protein, the function of which isn’t known.

The protein is normally cut into pieces by the body. But if it is cut up abnormally, one of the resulting fragments contains a portion scientists call beta-A4, or beta amyloid. This portion is found in the plaques in the brains of people with Alzheimer’s disease.

The gene fragment inserted in the mice included the part that gives rise to beta-A4, as well as surrounding segments. It also contained a segment from a different gene to ensure that the mouse brain cells would produce beta-A4 and adjacent portions of the amyloid protein.

At eight months of age, mice showed plaques and neurofibrillary tangles in certain parts of their brains. In chemical tests, these features reacted as their human counterparts do.

The mice also showed extensive loss of brain cells, the researchers said.

Behavioral changes included irritability, abnormal gait and posture, and a ″frenetic″ way of moving about, Gordon said. The mice haven’t yet been tested for problems in learning and memory, he said.

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