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Scientists Make Mice With Alzheimer-Like Disease, Should Aid Research

December 11, 1991

NEW YORK (AP) _ Scientists have created mice that develop a version of Alzheimer’s disease, a major step that should aid in studying the human version and finding treatments.

The brains of the mice contained abnormalities like those of Alzheimer’s: protein-bearing deposits called plaques, nerve cell abnormalities called neurofibrillary tangles and brain cell degeneration.

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

The mice, which developed the disease because researchers inserted a fragment of a human gene, also showed abnormal behavior, he said.

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

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

″I think this is very exciting work, and I think it’s a real step forward in research related to Alzheimer’s disease,″ commented 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. They show more Alzheimer-like brain changes than did mice reported earlier this year, he said.

About 4 million Americans, including about 10 percent of the population above age 65, are estimated to have Alzheimer’s disease. 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 is not 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 8 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 have not yet been tested for problems in learning and memory, he said.

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