Lithium Shows Promise for Treating Alzheimer's

By blocking an enzyme crucial to the formation of the plaques and tangles of Alzheimer's disease, lithium stems the accumulation of beta amyloid in mice, scientists have discovered. Their findings were reported in the May 22, 2003, issue of Nature.

The researchers first treated cells expressing the amyloid precursor protein with lithium, which they had earlier found blocks the enzyme glycogen synthase kinase-3 alpha (GSK-3 alpha). Therapeutic doses of lithium inhibited the production of beta amyloid and also blocked the formation of neurofibrilary tangles by the tau protein-3 inhibitor. Another GSK-3 alpha inhibitor, structurally unrelated to lithium, also reduced the production of beta amyloid. As expected, raising GSK-3 alpha levels enhanced beta amyloid production. Similar findings resulted from lithium treatment of mouse neurons and mice carrying mutations known to cause inherited Alzheimer's disease in humans.

"Although widely used to treat bipolar disorder, lithium's propensity to cause side-effects may limit its use in older people, who are more susceptible to Alzheimer's disease,” said lead researcher Peter Klein, M.D., of the University of Pennsylvania School of Medicine (Philadelphia, USA). It will be important to develop new agents that specifically target GSK-3 alpha, he added.

The researchers suggested that combination therapy with lithium and nonsteroidal anti-inflammatory drugs (NSAIDs) might have an enhanced effect in reducing beta amyloid levels, since certain NSAIDs have been shown to reduce beta amyloid levels.




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