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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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