Lithium deficiency is a possible cause of Alzheimer’s, according to a crucial study that provides a new disease theory and a novel strategy for its treatment. The authors, from Harvard University (USA), have shown that lithium, a scarce metal chemical element in the earth’s crust, plays an essential role in the functioning of the brain. Researchers have also observed that administering a salt, lithium orotate, mice prevents memory losses and characteristics pathological alterations. The signatories ask citizens who do not take supplements on their own, because they can be extremely dangerous, but they need to start clinical trials to investigate the effect of lithium orotate on people. Its results are published on Wednesday, one of the most prestigious scientific publications in the world.
The research leader, compares the Alzheimer’s with a chaotic battlefield covered with corpses after a war. There is so much destruction that it is difficult to know how everything started. Yankner himself discovered in 1990 that a protein that is deposited in people’s brains with Alzheimer’s, called, can cause the degeneration of neurons. Another protein, called Tau, ovillus shape within the brain cells of these patients. And the activation of immune cells maintains chronic neuroinflammation that damages neurons and deteriorates their connections. The battlefield in the brain is so confusing that, more than a century after the discovery of the disease in memory losses, the scientific community still does not understand how Alzheimer’s arises. “Lithium deficiency is the rupture in communication that leads to war,” Yankner explains to El País.
Harvard’s team wanted to illuminate the possible role of about thirty metal chemical elements, such as iron and copper, in the enigmatic process that leads to Alzheimer’s. The researchers analyzed conserved human samples at Rush University in Chicago, a collection with donations of thousands of healthy people or in different phases of cognitive deterioration. After measuring with unprecedented precision the very small traces of these metals, the group detected that only lithium levels were drastically reduced as the Alzheimer’s advanced. The finding fit previous studies that had observed a surprising fact: drinking water with greater amounts of lithium is associated with a lower incidence of dementia in the population. In Denmark, this effect was seen in an analysis of in 2017.
Yankner’s group explains that the characteristic deposits of beta amyloid protein bind to lithium and kidnap it, preventing their natural function in the brain. That drop in metal levels affects all fundamental brain cells, according to the neurologist. “Lithium deficiency is a possible common mechanism for multisystemic degeneration of the brain that results in dementia,” he says. The finding is transcendental, as Harvard University has stressed in. “The idea that lithium deficiency can be a cause of Alzheimer’s is new and suggests a different therapeutic approach,” says Yankner.
The role of lithium as a mood stabilizer is known – a century ago was an ingredient of the original recipe of – and is used as treatment for people with bipolar disorder, depression or schizophrenia. The most common drug is lithium carbonate, a substance that can cause kidneys and seizures. The Yankner team has discovered that another compound, the lithium orotate, is effective with a thousandth of the usual dose and does not remain captured in the deposits of the beta amyloid protein. This salt – formed by five carbon atoms, three of hydrogen, one of lithium, two of nitrogen and four oxygen (C₅h₃lin₂o₄) – prevents pathological alterations and memory losses both in mice that age naturally and other genetically modified to imitate the effects of Alzheimer’s effects, according to the experiments performed in Harvard.
“As a neuroscientist, it is fascinating to explore the functions of lithium in the brain. Our genetic analysis suggests that lithium affects all the main types of brain cells. I suspect that we have barely scratched the surface,” says Yankner, who continues to investigate to pave the path to future clinical trials of the lithium orotate in people.
The idea that lithium deficiency can be a cause of Alzheimer’s is new and suggests a different therapeutic approach
Bruce Yankner, Harvard neuroscientist
A Spanish study, led by biologists and showed in 2013 that lithium carbonate in transgenic mice and improved its memory. Vitoric emphasizes that Harvard’s team has now opted for a seemingly less toxic compound, but insists that no one takes it on their own. “Lithium is very dangerous, the dose must be controlled very well,” warns the researcher, professor at the University of Seville. Vitoric applauds the new study, but maintains caution until these hopeful results are confirmed in human trials. “It will not be the drug that cures the Alzheimer’s, but it may mitigate its symptomatology,” he says.
His colleague Antonia Gutiérrez emphasizes that Harvard’s work has established a relationship between lithium deficiency and activation towards a proinflammatory state of, immune cells of the brain, discovered in 1918 by the Spanish neuroscientist. The dysfunction of these cells prevents them from eliminating the harmful deposits of beta amyloid protein, which in turn would cause the advance of the neurodegenerative process through inflammation, the accumulation of tau protein ovillus and the loss of connections between neurons. “The results of this study would support the idea that lithium could be a microglial state modulator and, from this perspective, open a way to modulate the progression of the disease,” celebrates the biologist, professor at the University of Malaga.
Gutierrez, however, is skeptical of lithium deficiency is a cause of Alzheimer’s. “The suggestion that lithium is a key factor in the origin of the disease is somewhat speculative. Work does not determine whether lithium deficiency is a consequence or a primary factor of the disease,” says the professor. “The extrapolation of the results of this study to human pathology needs more scientific support. Most of the experiments were carried out in transgenic animal models, and direct causality has been demonstrated in humans,” says Gutiérrez. “If confirmed, the main challenge would be to find a safe and effective dose, since lithium can have toxic effects, especially in people with the committed renal function,” he adds.
The pathologist directs the brain bank of the one hundred foundation, with more than a thousand donated organs, in Madrid. “The relationship of lithium with Alzheimer’s already has a long history, but this study is really new and important,” he says. Radish especially values that the Harvard team has analyzed human fabric post mortembecause “reveals the importance of brain donation.” Its custody foundation the brain donated by Antonio Mercero, the creator of the series Blue summer y Guard Pharmacywho lived with Alzheimer’s the last years of his life.
Radish recalls that there are already two treatments, the and, that slow down between 27% and 35% the cognitive deterioration of Alzheimer’s patients, but are very expensive – per patient per year – and cause serious side effects. The pathologist emphasizes that the lithium orotate proposed by Yankner’s team could complement the modest efficacy of these two therapies, if their activity is confirmed in people. “It’s excellent news in the Alzheimer’s field,” Rábano celebrates.
