For years, scientists have been searching for the first spark that triggers Alzheimer’s disease, the most common cause of dementia.
They’ve also wondered why some people’s brains show signs of Alzheimer’s — such as abnormal protein build-up — yet they never lose their memory or thinking skills.
Now, researchers at Harvard Medical School think they might have found a surprising answer: a lack of lithium in the brain.
Lithium is best known as a medication for mood disorders like bipolar disorder. But this new research, published in Nature on August 6, reveals that lithium naturally exists in the human brain, helping to protect nerve cells and keep them working well.
The team found that lithium loss in the brain happens very early in Alzheimer’s disease, possibly before memory problems even begin.
The study, which took 10 years to complete, involved experiments on mice as well as tests on human brain tissue and blood samples from people at different stages of cognitive health.
In humans, lower brain lithium levels were linked to early memory decline. In mice, lithium depletion made Alzheimer’s-like brain changes appear faster and worsened memory problems.
The researchers discovered that in the early stages of Alzheimer’s, sticky amyloid beta proteins — one of the disease’s main hallmarks — bind to lithium, removing it from where it’s needed. Without enough lithium, many types of brain cells start to malfunction.
To test a solution, the team developed a special form of lithium called lithium orotate, which avoids being trapped by amyloid plaques. When mice with Alzheimer’s-like symptoms drank water containing lithium orotate, their memory returned and brain damage was reversed.
Alzheimer’s disease affects an estimated 400 million people worldwide. It’s marked by clumps of amyloid beta, tangles of another protein called tau, inflammation, and loss of protective brain proteins.
However, these features don’t fully explain why some people develop dementia and others don’t. Treatments aimed at removing amyloid beta have had only limited success, often slowing but not stopping cognitive decline. The new findings suggest that lithium might be a missing link in the puzzle, affecting many parts of the disease process at once.
To study lithium in humans, the Harvard team worked with the Rush Memory and Aging Project in Chicago, which stores brain tissue donated by thousands of people.
Using advanced testing methods, they measured levels of 30 different metals in the brains and blood of people with normal memory, mild cognitive impairment, and Alzheimer’s. Lithium was the only metal that changed significantly early in the disease, dropping sharply in those with memory problems.
In mouse experiments, a lithium-deficient diet led to faster brain aging, more inflammation, more amyloid plaques, and memory loss. Giving lithium orotate not only stopped the decline but also restored memory — even in older mice.
The researchers say this form of lithium worked at doses 1,000 times lower than the standard lithium carbonate used for mood disorders, making it much less likely to be toxic.
Although these results are promising, the team cautions that the findings are from animal studies and brain samples, not yet from large human trials.
People should not take lithium on their own, as high doses can be dangerous, especially for older adults. The next step will be clinical trials to see if low-dose, amyloid-evading lithium compounds can prevent or treat Alzheimer’s in people.
If future research confirms these findings, testing lithium levels could become a simple screening tool for early Alzheimer’s risk. Adjusting lithium to healthy brain levels might then help delay or even prevent dementia.
This study offers an exciting new perspective on Alzheimer’s. Unlike most current treatments that focus on a single problem — such as amyloid plaques or tau tangles — lithium appears to influence many processes at once.
It could explain why some people with “Alzheimer’s-like” brains never develop symptoms: they may naturally have enough lithium to protect their brain cells.
If lithium orotate proves safe and effective in humans, it could become a widely available, affordable tool for prevention and treatment. However, until human trials are done, this remains a hopeful but unproven approach.
If you care about Alzheimer’s disease, please read studies about These places in U.S. have the most cases of Alzheimer’s disease and findings of Scientists confirm the link between COVID-19 and Alzheimer’s disease.
For more information about Alzheimer’s disease, please read studies about New Alzheimer’s treatment: anti-inflammatory drug may prevent memory loss and findings of The diabetes drug surprise: a possible shield against Alzheimer’s?
The study is published in Nature.
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