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lite.cnn.com - on gopher - inofficial
ARTICLE VIEW:
Scientists say it may be possible to protect aging brains from
Alzheimer’s with an old remedy — lithium
By Brenda Goodman, CNN
Updated:
1:07 PM EDT, Fri August 8, 2025
Source: CNN
In a major new finding almost a decade in the making, researchers at
Harvard Medical School say they’ve found a key that may unlock many
of the mysteries of Alzheimer’s disease and brain aging — the
humble metal lithium.
Lithium is best known to medicine as a mood stabilizer given to people
who have bipolar disorder and depression. It was approved by the US
Food and Drug Administration in 1970, but it was used by doctors to
treat mood disorders for nearly a .
Now, for the first time, researchers have shown that lithium is
naturally present in the body in tiny amounts and that cells require it
to function normally — much like vitamin C or iron. It also appears
to play a critical role in maintaining brain health.
In a series of experiments reported Wednesday in the , researchers at
Harvard and Rush universities found that depleting lithium in the diet
of normal mice caused their brains to develop inflammation and changes
associated with accelerated aging.
In mice that were specially bred to develop the same kinds of brain
changes as humans with Alzheimer’s disease, a low-lithium diet revved
the buildup of sticky proteins that form plaques and tangles in the
brains that are hallmarks of the disease. It also sped up memory loss.
Maintaining normal lithium levels in mice as they aged, however,
protected them from brain changes associated with Alzheimer’s.
If further research supports the findings, it could open the door to
new treatments and diagnostic tests for Alzheimer’s, which affects an
estimated 6.7 million older adults in the United States, the US Centers
for Disease Control and Prevention.
A unifying theory of Alzheimer’s disease
The research provides a unifying theory that helps explain so many of
the puzzle pieces scientists have been trying to fit together for
decades.
“It is a potential candidate for a common mechanism leading to the
multisystem degeneration of the brain that precedes dementia,” said
Dr. Bruce Yankner, a professor of genetics at Harvard Medical School,
who led the study. “It will take a lot more science to determine
whether this is a common pathway… or one of several pathways,” to
Alzheimer’s, he added. “The data are very intriguing.”
In an editorial published in Nature, Dr. Ashley Bush, a neuroscientist
who directs the Melbourne Dementia Research Center at the University of
Melbourne in Australia, said the researchers “present compelling
evidence that lithium does in fact have a physiological role and that
normal aging might impair the regulation of lithium levels in the
brain.” He was not involved in the study.
Close examination of human and animal brain tissues, along with genetic
investigations in the study, found the mechanism that appears to be at
play: Beta amyloid plaques — the sticky deposits that gum up the
brains of Alzheimer’s patients — bind to lithium and hold it,
including the type that’s normally present in the body, as well as
the commonly prescribed form. This binding depletes lithium available
for nearby cells, including important scavengers known as microglia.
When the brain is healthy and functioning normally, microglia are waste
managers, clearing away beta amyloid before it can accumulate and can
cause harm. In the team’s experiments, microglia from the brains of
lithium-deficient mice showed a reduced ability to sweep away and break
down beta amyloid.
Yankner believes this creates a downward spiral. The accumulation of
beta amyloid soaks up more and more lithium, further crippling the
brain’s ability to clear it away.
He and his colleagues tested different lithium compounds and found one
— lithium orotate — that doesn’t bind to amyloid beta.
When they gave lithium orotate to mice with signs of Alzheimer’s in
their brains, these changes reversed: Beta amyloid plaques and tangles
of tau that were choking the memory centers of the brain were reduced.
Mice treated with lithium were once again able to navigate mazes and
learn to identify new objects, whereas those who got placebos showed no
change in their memory and thinking deficits.
Don’t try this at home
In its natural form, lithium is an element, a soft, silvery-white metal
that readily combines with other elements to form compounds and salts.
It’s naturally present in the environment, including in food and
water.
Scientists have never fully known how it works to improve mood — only
that it does. The original formula for 7Up soda included lithium — it
was called 7Up Lithiated Lemon Soda — and as a hangover cure and mood
lifter “for hospital or home use.” Some hot springs known to
contain mineral water brimming with lithium became sought out for their
curative powers.
In the large doses used to treat mood disorders, lithium “is a drug
we know very, very well, and we also know it’s a dangerous drug,
especially for older people. Overdoses are easy,” said Dr. Kostas
Lyketsos, who directs the Memory and Alzheimer’s Treatment Center at
Johns Hopkins Medicine. “You might be taking a stable dose and have
no side effects and you get really dehydrated in the hot sun, and it
becomes toxic.”
It has to be monitored closely because it can damage the kidneys,
especially when taking in combination with other drugs like
non-steroidal anti-inflammatory drugs like ibuprofen.
“Is there a future in which lithium at a very low dose could
supplement what seems to have been lost? Possibly. How do you prove
that? I don’t know,” said Lyketsos, who was not involved in the
research. That will be the work of future studies.
While the science is exciting, “this is still very early,” Lyketsos
said.
The normal amounts of lithium in our bodies, and the concentrations
given to the mice in the new study, are small — about 1,000 times
lower than doses given to treat bipolar disorder, Yankner notes. Tests
of the mice given low doses of lithium orotate showed no signs of
damage.
That’s encouraging, Yankner said, but it doesn’t mean people should
try to take lithium supplements on their own.
“A mouse is not a human. Nobody should take anything based just on
mouse studies,” Yankner said.
“The lithium treatment data we have is in mice, and it needs to be
replicated in humans. We need to find the right dose in humans,” he
added.
Yankner said he hoped toxicity trials of lithium salts would start
soon. Neither he nor any of his co-authors have a financial interest in
the outcome of the research, he said.
The National Institutes of Health was the major funder of the study,
along with grants from private foundations.
“NIH support was absolutely critical for this work,” Yankner said.
Evidence builds for lithium’s role in aging
The new research corroborates earlier studies hinting that lithium
might be important for Alzheimer’s. A large Danish study found people
with higher levels of lithium in their drinking water were less likely
to be diagnosed with dementia compared with those whose tap water
contained naturally lower lithium levels. Another published in 2022
from the United Kingdom found that people prescribed lithium were about
half as likely has those in a control group to be diagnosed with
Alzheimer’s, suggesting a protective effect of the drug.
But lithium’s use in psychiatry caused it to become type cast as
therapeutic, Yankner said. No one realized it might be important to the
body’s normal physiology.
That happened in part because the amounts of lithium that typically
circulate in the body are so small, they couldn’t be quantified until
recently. Yankner and his team had to adapt new technology to measure
it.
In the first stage of the research, the scientists tested the brain
tissue and blood of older patients collected by the brain bank at Rush
University for trace levels of 27 metals. Some of the patients had no
history of memory trouble, while others had early memory decline and
pronounced Alzheimer’s. While there was no change in the levels of
most metals they measured, lithium was an exception. Lithium levels
were consistently lower in patients with mild cognitive impairment or
Alzheimer’s compared to those with normal brain function. The brains
of patients Alzheimer’s disease also showed increased levels of zinc
and decreased levels of copper, something scientists had observed
before.
Consistently finding lower lithium levels in the brains of people with
memory loss amounted to a smoking gun, Yankner said.
“At first, frankly, we were skeptical of the result because it
wasn’t expected,” said Yankner.
But it held up even when they checked samples from other brain banks at
Massachusetts General Hospital, Duke and Washington universities.
“We wanted to know whether this drop in lithium was biologically
meaningful, so we devised an experimental protocol where we could take
lithium selectively out of the diet of mice and see what happens,”
Yankner said.
When they fed the mice a low-lithium diet, simply dropping their
natural levels by 50%, their brains rapidly developed features of
Alzheimer’s.
“The neurons started to degenerate. The immune cells in the brain
went wild in terms of increased inflammation and worse maintenance
function of the neurons around them, and it looked more like an
advanced Alzheimer patient,” Yankner said.
The team also found the gene expression profiles of lithium-deficient
mice and people who had Alzheimer’s disease looked very similar.
The researchers then started to look at how this drop in lithium might
occur. Yankner said in the earliest stages there’s a decrease in the
uptake of lithium in the brain from the blood. They don’t yet know
exactly how or why it happens, but it’s likely to be from a variety
of things including reduced dietary intake, as well as genetic and
environmental factors.
The major source of lithium for most people is their diet. Some of the
foods that have the most lithium are leafy green vegetables, nuts,
legumes and some spices like turmeric and cumin. Some mineral waters
are also rich sources.
In other words, Yankner said, a lot of the foods that have already
proven to be healthy and reduce a person’s risk of dementia may be
beneficial because of their lithium content.
“You know, oftentimes one finds in science that things may have an
effect, and you think you know exactly why, but then subsequently turn
out to be completely wrong about why,” he said.
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