Reversing Alzheimer’s Disease May Reveal Lithium as Potential Key, Research Shows
Reversing Alzheimer’s Disease May Reveal Lithium as Potential Key, Research Shows
A team of Harvard Medical School (HMS) researchers says they have found a way to reverse Alzheimer’s disease and restore brain function by using low doses of lithium.
After nearly a decade of investigation, the Harvard scientists discovered that the depletion of lithium plays a major role in developing Alzheimer’s disease. What’s more, the team says they have proven, for the first time, that lithium naturally occurs in small amounts in the body and cells need it to function normally.
“The idea that lithium deficiency could be a cause of Alzheimer’s disease is new and suggests a different therapeutic approach,” senior author Bruce Yankner, professor of genetics and neurology in the Blavatnik Institute at HMS, stated in a news release.
Although the Harvard researchers used mice as part of their study, the investigators are optimistic that their findings could lead to earlier detection of Alzheimer’s in humans, new treatments for Alzheimer’s by addressing lithium deficiency in the brain, and a broader understanding of how the brain ages.
Lithium is a soft, shiny, silvery-white metal. It is the lightest known metal and can store energy at high density and discharge electrons rapidly.
“This is the basis of the lithium battery that powers our phones, laptops, and electric vehicles,” Yankner explained to The Washington Post.
Although the connection between lithium deficiency and Alzheimer’s disease may be a novel concept, lithium has been previously investigated as a potential treatment for Alzheimer’s and anti-aging medication. A 2017 study in Denmark suggested that the presence of lithium in drinking water might be linked to a lower incidence of dementia in the population.
Lithium has also been used for decades in various ways. For example, lithium was once included in the original formula for the 7Up soft drink (marketed then as Bib-Label Lithiated Lemon-Lime Soda) until the U.S. Food and Drug Administration (FDA) banned lithium citrate in soft drinks in 1948.
In 1970, however, the FDA approved a form of lithium, lithium carbonate, in the treatment of bipolar disease. It is believed to be a mood stabilizer and can also be prescribed for long-term treatment of depression.
“It’s been around for decades, and we have a lot of research and a lot of evidence supporting its use,” Elizabeth Hoge, a professor of psychiatry at Georgetown University School of Medicine, told The Washington Post. “The most important thing is that it does help patients. We know that it works from randomized, controlled trials.”
Hoge said that using lithium requires monitoring renal and thyroid functions, which can decline in some cases.
The HMS Research Team’s Findings
For their study, published in the journal Nature, HMS researchers used mice bred to develop brain changes similar to those observed in humans with Alzheimer’s disease. The investigators noticed that when they reduced the lithium in the mice’s diet, they lost brain synapses and began to experience memory loss.
The mice that had started losing their memory were then given a potent compound called lithium orotate, enough to replicate the natural lithium levels in the brain. The compound reversed Alzheimer’s, prevented brain damage, and restored memory, according to the research team.
In addition to the experiment in mice, the Harvard team analyzed more than 500 human brain tissues and blood samples from the Rush Memory and Aging Project in Chicago and other brain banks. The human brains examined were from individuals at various stages of cognitive health.
Yankner said that having this resource was critical because “trying to study the brain in the late stages of Alzheimer’s is like looking at a battlefield after a war. There’s a lot of damage, and it’s hard to tell how it all started.”
Yankner’s team discovered that the naturally occurring lithium in the brain is 1,000 times less than the lithium provided in medications to treat bipolar disorder.
How Lithium Works
Studies have found that in a healthy brain, lithium supports the connections and communication pathways that allow neurons to communicate effectively with one another. Research also shows that lithium contributes to the formation of myelin, the coating that insulates these pathways, and helps microglial cells clear cellular debris that can disrupt brain function.
The loss of lithium speeds up the formation of amyloid beta plaques and tau tangles that interfere with communication between nerve cells. The plaques can trap lithium and reduce its ability to support brain function.
According to Yankner and his team, lithium ornate helped the mice decrease the production of amyloid plaques and tau tangles, which allowed the microglial cells to remove the plaques more effectively. In the 1990s, Yanker was the first to demonstrate that amyloid beta is toxic.
Amyloid beta is a protein that builds up in the brains of people with Alzheimer’s disease. The protein clumps together in the brain to form plaques between neurons, which interfere with normal brain function.
Scientists believe amyloid beta plaques and neurofibrillary tangles of the protein tau are primary contributors to the development of Alzheimer’s disease. However, the Harvard researchers say these key factors “never explained the full story of the disease.” For example, some individuals with these abnormalities do not show any signs of cognitive decline.
While there are new treatments that target amyloid beta, there are no medications that have been able to stop or reverse Alzheimer’s disease, a neurodegenerative condition that affects seven million people 65 and older in the United States. Alzheimer’s is the most common form of dementia and a progressive disease that causes a loss of cognitive functions, including memory, thinking, and reasoning. The disease gradually disrupts an individual’s quality of life and independence and ultimately leads to death.
The study’s results from Yankner’s team and researchers at Boston Children’s Hospital and the Rush Alzheimer’s Disease Center in Chicago suggest that measuring lithium levels may help doctors screen people for signs of Alzheimer’s disease well in advance of symptoms appearing.
Yankner said doctors might be able to measure lithium levels in the cerebrospinal fluid or blood, or through brain imaging.
While lithium was a key factor in reversing Alzheimer’s in mice, Yankner warns against individuals taking lithium themselves because it is not clear whether it would produce the same effect in humans.
“I do not recommend that people take lithium at this point, because it has not been validated as a treatment in humans,” Yankner told The Washington Post. “We always have to be cautious because things can change as you go from mice to humans.” Yankner also stated that their study results still need to be confirmed by other laboratories.
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