A study opens a window of hope for treating Alzheimer's with lithium.

BarcelonaA study from Harvard Medical School has found that the loss of lithium, a metallic chemical element, could be one of the first changes that lead to Alzheimer's. According to the finding, the brain naturally produces this metal, which serves to protect it from neurodegeneration. The findings, published in the journal Nature, thatThe results, which took ten years to obtain, are based on a series of experiments with mice, analyses of human brain tissue, and blood samples from people at various stages of cognitive health. However, the authors caution that the experiment is still in a preliminary phase and may not be applicable to humans.

The results, which unify decades of observations in patients, provide a new theory about the disease and a new strategy for early diagnosis, prevention, and treatment. But how does this finding change current research? Until now, Alzheimer's involved a series of brain abnormalities, such as accumulations of the protein beta amyloid, neurofibrillary buds of the protein tau, and the loss of a protective protein called REST. According to the study's authors, lithium could have been the "missing link" until now.

"The idea that lithium deficiency might be a cause of Alzheimer's disease is new and suggests a different therapeutic approach," says Bruce Yankner, who in the 1990s was the first to demonstrate that amyloid beta is toxic. Thus, Yankner says, the study raises "hope" that researchers may one day use lithium to treat the disease, rather than focusing on either the amyloid beta protein or the tau protein.

Lithium orotat

One of the study's key findings is that as amyloid beta begins to form deposits in the early stages of dementia, both in humans and animal models, it binds to lithium, reducing lithium function in the brain. Lower lithium levels affect all major brain cell types and, in mice, result in changes reminiscent of Alzheimer's disease, including memory loss. In fact, the authors have identified a class of lithium compounds that can prevent this. Treating mice with lithium orotat reportedly reversed Alzheimer's disease pathology, prevented brain cell damage, and restored memory.

Although the findings need to be confirmed in humans through clinical trials, they suggest that measuring lithium levels could help detect Alzheimer's in its earliest stages. Furthermore, they also point to the importance of testing lithium compounds that prevent amyloid for treatment or prevention. Today, other lithium compounds are already used to treat bipolar disorder, for example, but they are administered at much higher concentrations, which can be toxic, especially for older people, according to the same statement.

Yankner's team found that lithium orotat is effective at one-thousandth of this dose, enough to mimic the natural level of lithium in the brain. Mice treated for almost their entire adult life would not have shown signs of toxicity at this dose. "You have to be careful when extrapolating results from mouse models, and you never know until you test it in a controlled clinical trial in humans, but so far the results are very encouraging," Yankner says.