A recent study from Harvard Medical School asks whether the element lithium might be a key factor in whether someone develops Alzheimer’s disease.
Led by Dr. Bruce Yankner, professor of genetics and neurology at Harvard Medical School, the almost-decade long study says it is the first to show that lithium is found naturally in the brain in small amounts and suggests that the element plays an important role in the prevention and treatment of cognitive decline.
The study published in Nature this month found a link between lithium deficiency in the brain and an increase in amyloid plaques and tau tangles — known contributors to the development of Alzheimer’s disease. In trials on mice, researchers found they were able to reverse the disease, prevent brain cell damage and restore memory loss through a small dosage of a lithium compound called lithium orotate.
Experts told PBS News that it’s premature to conclude from the results that people should use lithium as a treatment or prophylactic for Alzheimer’s disease — but if the findings are confirmed through a randomized human controlled trial, measuring lithium levels could potentially help with early detection of the disease and provide a broader understanding of aging brains.
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“My hope is that if lithium worked out, it might actually restore function, not only change the slope of decline. It certainly does that in the advanced mouse models,” Yankner said. “So I’m optimistic, but we have to hold judgment until we see what happens in people.”
What is lithium and how is it used?
Lithium is a naturally occurring element in the same family as sodium and potassium. The alkali metal is soft and silvery, and used for a variety of purposes, from nuclear power to ceramics, but most famously in batteries.
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The metal has also been used as a mood stabilizer for people with bipolar and other mood disorders since the 1900s. 7 Up sodas even contained lithium citrate from 1929 to the 1940s, until the FDA banned the compound from all soda and beer due to reports of overuse leading to lithium toxicity, including symptoms such as nausea, vomiting and kidney damage.
Past studies have considered lithium as a factor in dementia and Alzheimer’s disease.
A 2017 Danish study found there was a possible link between lower rates of dementia in certain regions of Denmark and “microlevels” of lithium in the drinking water, suggesting “even exposure to slightly higher lithium levels over a longer period of time can have a potentially major impact on dementia,” Yankner said.
What the study found about lithium
Jason Choi, Zhen Kai Ngian, Dr. Bruce Yankner, Monlan Yuan and Liviu Aron in their Harvard research lab on Aug. 4, 2025. The authors of a recent medical paper in Nature found that lithium may help protect against brain aging and Alzheimer’s disease. The authors of the paper pose for a portrait Photo by Heather Diehl/The Boston Globe via Getty Images
The new study used postmortem brain tissue from the Memory and Aging Project by Rush University in Chicago, donated by thousands of study participants ranging across all levels of the cognitive disease.
Using advanced tools that could detect trace amounts of metals in the brain and blood — something that older machines were not sensitive enough to do in the past — Yankner’s team found that donors with mild impairment and advanced Alzheimer’s had lower lithium levels compared to cognitively healthy people.
For donors with early signs of memory loss, “the lithium levels were one of the first things to drop,” Yankner said. “And also full-blown Alzheimer’s disease, we saw a few metals had changed, just as other people had seen. But the most significant change was actually in this natural level of lithium.”
The researchers also experimented with restricting the lithium intake of normal mice and Alzheimer’s mice – mice that model Alzheimer genes found in humans. They found that in healthy mice, a lithium-deficient diet accelerated cognitive decline, loss of synaptic connections between neurons and memory loss. In the Alzheimer’s mice, the formation of amyloid plaques – clumps of sticky protein that disrupt brain function that are trademarks of Alzheimer’s disease – was accelerated.
Yankner and his colleagues discovered that lithium gets depleted in the brain when amyloid plaques bind to the metal, which reduces the lithium’s availability to other necessary brain functions, like microglia cells that mount immune responses and repair damage.
Microglias are the “scavengers or macrophages of the brain,” Yankner said, and one of their key functions is to clear the amyloid plaques. The researchers discovered that in a lithium-deficient brain, microglia were not able to perform their function.
The team tried out various lithium compounds on the mice. The amyloid plaques were found to bind to lithium carbonate, the compound commonly prescribed for mood disorders, making it less effective in preventing the development of Alzheimer’s.
In previous clinical trials, lithium carbonate had shown some efficacy in fighting the disease, but the high dosage used can be toxic to older people.
Lithium orotate, which is currently marketed as a dietary supplement for people, avoided being bound by the amyloid plaques in the study by Yankner’s team. Using a dose of lithium orotate on mice at one-thousandth the clinical dose of lithium carbonate showed to be the most effective treatment so far for reversing memory loss in the studied animals without causing toxicity, Yankner said.
Can taking a lithium supplement prevent Alzheimer’s disease?
Don’t start taking a lithium supplement just yet.
Mice studies do not always reflect human trials, according to Rachel Whitmer, professor of public health sciences and neurology at UC Davis.
“How you translate to applying that experiment [in mice] to humans is more complicated and takes longer, but with the right planning, it can absolutely happen and it can absolutely be successful,” said Whitmer.
Yankner added that his team is exploring “whether lithium orotate is the best we can do.”
“Using the screening approach and platform we’ve developed, we might even be able to find a better lithium compound,” he said.
Dr. Ronald Petersen, director of the Mayo Clinic Alzheimer’s Disease Research Center and the Mayo Clinic Study of Aging, said it is too early for people to alter their diets or use a lithium replacement for a potential approach to prevent and treat Alzheimer’s disease. He recommended watching the next stages of this line of research as it “may be a potential insight into one of the therapeutic pathways,” he said.
What comes next?
There have been major advances in Alzheimer’s research, according to Whitmer. In the past, one of the only ways to identify the disease was finding tau tangles and amyloid plaques in the brain during an autopsy.
Fast forward to today, and medical researchers have developed tests to detect biomarkers – biological molecules found in blood that can indicate the presence of conditions or diseases – for Alzheimer’s in living patients. Health care providers can also perform brain imaging and lumbar punctures, to determine if a person has abnormal levels of amyloid and tau in the brain.
Much more recently, plasma markers, which are blood-based biomarkers, have suggested to scientists that underlying pathologies in the brain can be seen in blood, according to Petersen.
Yankner said the next steps will be determining whether there is an effective dose of lithium orotate or another lithium compound for humans that treats Alzheimer’s with minimal toxicity, as well as finding a diagnostic blood test that can reliably identify lithium deficiency.
Similar to how risk factors for diabetes or heart disease can show up in blood tests today, Yankner envisions a future where people can learn if they are at risk for Alzheimer’s from their annual physical with a primary care provider.
“If one had a way of examining the lithium status of a person, that might dictate very early treatment,” Yankner said.
Laura Santhanam contributed reporting.
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