Lithium may fend off Alzheimer's disease
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.