http://www.cnn.com/2003/HEALTH/conditions/05/22/lithium.alzheimers.ap/index.html

Lithium eyed as Alzheimer's treatment

Mice experiments show drug blocks buildup of brain deposits

Thursday, May 22, 2003 Posted: 10:45 AM EDT (1445 GMT)

(AP) -- Lithium, used for decades to treat manic depression, has been shown in mice to block the production of proteins that form deposits in the brains of Alzheimer's patients, suggesting a potential role for the drug in treating the disease.

The researchers who conducted the experiments stressed that lithium has not been shown to work on Alzheimer's patients.

And lithium, though widely used to treat mental illness, has many side effects, including kidney damage. The problems are most pronounced in the elderly, who also face the greatest risk of Alzheimer's.

Alzheimer's is marked by the buildup in the brain of one protein, called amyloid beta, outside nerve cells and a second, called tau, that forms tangles in the cells. Alzheimer's affects about 12 million people worldwide.

Other possible approaches, including an experimental vaccine, have blocked the production of either amyloid beta or tau; lithium appears to tackle both, said the study's co-author, Dr. Peter Klein of the University of Pennsylvania.

Details of the mouse experiments appear in Thursday's issue of the journal Nature.

"Potentially, lithium could be used to reverse both the pathological features of Alzheimer's disease," Klein said.

Other scientists said the findings were encouraging, in part because lithium is a known drug.

"It seems you could block with a single medicine both of the major structural manifestations of the disease. This would be the first time that has been shown," said Dr. Sam Gandy, director of the Farber Institute for Neurosciences at Thomas Jefferson University in Philadelphia.

Zaven Khachaturian, senior science adviser to the Alzheimer's Association, said: "The chemistry of it is very exciting, very tantalizing."

Klein and his colleagues used mice bred to overproduce a protein that when modified forms amyloid beta. Many scientists believe that the buildup of amyloid beta causes the debilitating effects of the memory-robbing disease. The mouse experiments showed that lithium disrupts that modification process.

Klein and colleagues also showed that lithium disrupts the modification of tau. While it is unclear what role tau plays in cells, the protein invariably piles up in lockstep with the progression of Alzheimer's.

Lithium targets an enzyme called GSK-3 that facilitates the modification of both the proteins found in Alzheimer's patients. Identification of GSK-3 as a target could pave the way for other drugs that disrupt the production of both proteins, Klein said.

Another advantage to lithium is that it does not disrupt the processing of another protein called notch, as do other potential Alzheimer's drugs. Notch is vital for the production of blood cells.

Khachaturian, former director of the office of Alzheimer's research at the National Institutes of Health, said he envisions studies that would look at the prevalence of Alzheimer's in people who already take lithium to control the mood swings associated with manic depression.