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Lithium may fend off Alzheimer's disease

July 27, 2004 By Helen Pilcher This article courtesy of Nature News.

Manic depression therapy could prevent brain degeneration.

Lithium, a common treatment for manic depression, might also help to stave off Alzheimer's disease. Patients who take the drug to stabilize their mood disorder are less likely to succumb to dementia, a study reveals.

For the last 30 years, lithium has been used to control the mood swings of patients with bipolar disorder, also known as manic depression. But over the last decade, an increased understanding of how the drug works has widened the scope for its use. Researchers now think that the simple salt could slow the progress of degenerative brain disorders, such as Huntington's and Alzheimer's disease.

Paula Nunes and colleagues from the University of São Paulo, Brazil, studied 74 elderly people with bipolar disorder. Four percent of those taking lithium had Alzheimer's disease, compared with 21% of patients who were not taking the drug.

The researchers conclude that lithium therapy may lower the risk of developing Alzheimer's disease. They presented their data at the 9th International Conference on Alzheimer's Disease and Related Disorders in Philadelphia, Pennsylvania, last week.

"The numbers are small, so it's difficult to draw any firm conclusions," says Alzheimer's researcher Bart De Strooper from the University of Leuven, Belgium. But the results do back up tissue culture and animal studies, which hint that lithium can tackle the two hallmarks of Alzheimer's disease, namely tangles and plaques.

Tangled up

Tangles are spaghetti-like filaments of a protein called tau, which build up inside cells making it difficult for them to work.

When mice with tangles are treated with lithium for five months, brain tau levels decrease dramatically, Takeshi Ishihara from Okayama University Graduate School of Medicine and Dentistry, Japan, and colleagues reported at the same conference last week.

The team think that the drug works by blocking the action of an enzyme called GSK-3. In a brain with Alzheimer's, GSK-3 seems to prompt the addition of phosphate molecules to the tau protein, causing tangles to form. Lithium may prevent this from happening.

The drug also helps to rid the rodent brain of plaques, the insoluble protein deposits that build up around neurons, impairing their ability to communicate. In mice genetically engineered to be prone to plaques, lithium inhibits GSK-3, stops the protein from building up and cuts the number of plaques.

Root of the problem

Therapies for Alzheimer's disease are desperately needed. Some 18 million people worldwide suffer from dementia, and the chances of succumbing to Alzheimer's, the most common form, rise rapidly with age. Half of those over 85 show symptoms.

Most drugs manage the symptoms of dementia rather than tackling the disease itself. But lithium, or drugs like it, could tackle the fundamental changes in the brain that cause the condition.

Lithium itself might not be suitable for elderly patients, advises Ishihara. Long-term treatment can cause nausea, vomiting, diarrhoea, and tremors, which older patients may find hard to tolerate. So, many drug companies are working on developing lithium-like drugs that inhibit GSK-3 but are free of the most serious side-effects.


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