Alzheimer's, lithium deficiency could play a role

From the laboratories of Harvard Medical School in Boston, Massachusetts, comes a glimmer of hope for Alzheimer's disease: a team of neuroscientists has discovered that lithium is naturally present in the brain, that its deficiency is associated with the typical signs of the disease, and that restoring its levels could protect against brain aging. And even reverse it. The study is published in the journal Nature , and—it should be noted right away—it's still very preliminary, meaning it was conducted only on mice and human brain tissue. The results should therefore be taken with a grain of salt: the research suggests lithium deficiency in the brain as a possible risk factor for dementia and a potential therapeutic target.

The role of lithium

Praised in the 19th century for its many health and mood-boosting benefits (it even appears as a stimulant in one of the first recipes for 7-Up, according to Nature News ), lithium has been used since the 1970s as a treatment for bipolar disorder and as a mood stabilizer. The scientific community soon noticed that, among people with bipolar disorder, brain aging appeared to be slower in those taking lithium than in those who did not. Meanwhile, epidemiological studies had shown that populations living in regions where water supplies contained trace amounts of lithium had relatively lower rates of dementia. Clinical trials testing lithium's effects on dementia, however, have so far yielded conflicting results. The new study follows this trend and demonstrates, for the first time, that lithium is naturally present in the brain, where it plays an important physiological role.

Lithium deficiency and cognitive decline

Several studies have so far reported dysregulation of metal ion levels in the cerebral cortex of people with Alzheimer's. Based on this knowledge, the authors analyzed the levels of 27 different metals. As an article in Nature News and Views explains, although the amount of zinc, a metal abundant in the healthy brain, was increased and that of copper was decreased in subjects with Alzheimer's (as previously found), lithium was the only metal with significantly reduced levels compared to those in the blood.

After conducting a series of experiments on mice and analyzing human brain tissue, Bruce Yankner and colleagues observed that when lithium concentrations in the brain decrease, memory loss and the characteristic neurological signs of Alzheimer's disease, namely amyloid plaques, develop. Specifically, lithium levels were lower in areas of the human brain affected by the disease than in unaffected regions. Furthermore, they observed that the metal binds to amyloid plaques, reducing the amount available for brain function. This, the authors hypothesize, could trigger a vicious cycle: less lithium in the brain leads to more amyloid plaques, which in turn leads to even less lithium. Indeed, the scientists report that lithium deficiency worsens as the disease progresses.

A possible therapeutic strategy

The next step was to attempt administering lithium to the animals. Instead of using lithium carbonate, which is tested in most clinical studies and is easily trapped by amyloid plaques, they tested low doses of lithium orotate. Studies suggest that the compound can lead to repair of the damaged area and memory recovery, without showing any toxicity. Obviously, all of this will need to be demonstrated in human clinical trials.