Muscle Disorder May Be Form of Alzheimer’s Disease : Medicine: USC researchers say an abnormal protein, beta-amyloid, shows up in both illnesses. It is the first time that it has been found in a disorder that does not involve the brain.
USC researchers have discovered that a relatively common muscle disorder may be a form of Alzheimer’s disease that strikes muscle cells rather than brain cells.
Both diseases are characterized by deposits of an abnormal protein, called beta-amyloid. The discovery of the protein in the muscle disease marks the first time that beta-amyloid has been found in a disease that does not involve the brain, Dr. Valerie Askanas, a USC neurologist, and her colleagues report today in the American Journal of Pathology.
Askanas predicted that the finding will lead to new insights into Alzheimer’s disease.
The muscle disorder, called inclusion-body myositis (IBM), is characterized by a disabling deterioration of muscle tissue and is believed to be the most common muscle disorder in people over 50, she said.
Askanas and her colleagues, Dr. W. King Engel and Dr. Renate B. Alvarez, studied biopsied muscle tissue from 11 patients with inclusion-body myositis. The samples showed the presence of beta-amyloid deposits in the tissue of all 11 patients. But they could not find beta-amyloid in muscle tissue from 14 other people who were either healthy or had other muscle diseases.
Because muscle cells can be grown readily in the laboratory while brain cells cannot, the discovery should make it much easier for researchers to study the mechanisms--identical, Askanas believes--of the two diseases. Askanas has shown that the defective cells can be grown in the laboratory and she hopes that this could lead to the development of new drugs to treat both conditions.
Askanas’ discovery is “very significant because this can give you a tool to do genetic studies on the responsible protein,” said Dr. Marinos Dalakas, a neurologist at the National Institute on Neurologic and Communicative Diseases.
But Dr. George Glenner, a neurologist at UC San Diego, cautioned that Askanas is a long way from proving that the two diseases have the same mechanism. “It might provide insight into Alzheimer’s or it might not,” he said. “The fact that she can grow the cells in tissue culture may very well help her understand her disease, but it may not have any relation to what is going on in Alzheimer’s.”
Alzheimer’s disease is characterized by memory loss, disorientation, depression and deterioration of bodily functions. It affects about 4 million Americans, most over 65, and causes 100,000 deaths annually.
The most noticeable biological sign of Alzheimer’s is the presence of plaques composed of beta-amyloid in the regions of the brain that control memory and learning. A growing body of evidence suggests that formation of these plaques physically damages brain cells, causing the symptoms of the disease.
Similar plaques have been found during autopsies of the brains of victims of Down’s syndrome as well as in those of people over 85 who died of causes other than Alzheimer’s. Researchers also have found the plaques in skin and intestinal cells of Alzheimer’s patients, but the plaques do not proliferate when such tissues are grown in the laboratory, suggesting that they are a byproduct of the disease process.
Researchers have long sought beta-amyloid deposits in muscle tissue from Alzheimer’s patients, but without success. Askanas sought them in inclusion-body myositis cells because of certain similarities between inclusion-body myositis and Alzheimer’s.
Myositis is a general term that refers to swelling and weakening of muscle tissues. In inclusion-body myositis, this swelling is associated with the presence of “inclusion bodies,” small, cystlike particles whose contents were previously unknown. Over time, the disorder produces pronounced disability much like muscular dystrophy, Askanas said. About 5% of patients respond to the steroid prednisone, but there is no form of effective treatment for the other 95%.
Askanas noted that there are several important similarities between Alzheimer’s and inclusion-body myositis. Both exhibit “sporadic” and genetic forms. The genetic forms run in families and strike at a relatively early age. The sporadic forms seemingly strike at random and affect older people. “You could call IBM a form of ‘peripheral Alzheimer’s disease,’ ” she said.
One of the patients the USC group studied had the genetic form of inclusion-body myositis, while the other 10 had the sporadic form. The team found no differences between the two.
But the most important aspect of the research, Askanas said, is that the inclusion-body myositis muscle cells can be grown in culture and that the beta-amyloid deposits are passed to successive generations of cells, indicating that the defect is genetic in origin. For the first time, “a living model of the disease can be established,” she said.
These laboratory grown cells can be used to track down the genetic defect that causes the disorder, a process that is under way. And once the disease process is better understood, they can be used to test new therapies, hopefully for inclusion-body myositis and Alzheimer’s.
