New advances in Alzheimer's treatment: a lithium compound restores memory in mice

Lithium is produced naturally in the brain, protects it from neurodegeneration, and maintains normal function of all major brain cell types, according to a study that found that loss of this element is one of the first changes that lead to Alzheimer's .

The findings, which took 10 years to develop, 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.

They are published in Nature , in an article that also describes a lithium compound that restores memory in animal models.

However, the authors caution, these are preliminary experiments and cannot be extrapolated to humans . These experiments require confirmation through clinical trials.

The results, according to those responsible for this study at Harvard Medical School, unify decades of observations in patients, providing a new theory about the disease and a new strategy for early diagnosis, prevention, and treatment.

Alzheimer's disease, which affects an estimated 400 million people worldwide, involves a range of brain abnormalities, including accumulations of the protein beta amyloid , neurofibrillary tangles of the protein tau, and the loss of a protective protein called REST , but these have never explained the "full story" of the disease.

For example, some people with these abnormalities show no signs of cognitive decline. Furthermore, recently developed treatments targeting amyloid beta typically fail to reverse memory loss and only modestly slow the rate of decline, according to a Harvard statement.

It's also clear that genetic and environmental factors influence Alzheimer's risk , but scientists haven't figured out why some people with the same risk factors develop the disease and others don't.

According to the study's authors, lithium could be the crucial "missing link ." "The idea that lithium deficiency could be a cause of Alzheimer's disease is new and suggests a different therapeutic approach," says Bruce Yankner, who was the first to demonstrate in the 1990s that beta amyloid is toxic.

The study raises "hope" that researchers may one day be able to use lithium to treat the entire disease, rather than focusing on just one aspect, such as beta amyloid or tau, he adds.

One of the study's key findings is that as beta amyloid 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 recapitulating Alzheimer's disease, including memory loss. The authors identified a class of lithium compounds that can prevent this.

Treating mice with a potent amyloid-evading drug called lithium orotate reversed Alzheimer's disease pathology, prevented damage to brain cells, 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 early stages. They also point to the importance of testing lithium compounds that prevent amyloid for its treatment or prevention.

Other lithium compounds are already used to treat bipolar disorder and major depressive disorder , but they are administered in much higher concentrations that can be toxic, especially for older people, the same statement notes.

Yankner's team found that lithium orotate was effective at one-thousandth of that dose, enough to mimic the natural level of lithium in the brain. Mice treated for almost their entire adult life showed no signs of toxicity.

"You have to be careful when extrapolating results from mouse models, and you never know until you test it in a controlled human clinical trial," Yankner cautions. "But so far the results are very encouraging."