A new study from Harvard Medical School and Rush University is shedding light on a surprising potential ally in the fight against Alzheimer’s disease: lithium. Known primarily as a mood stabilizer for bipolar disorder and depression, lithium may also play a vital role in brain health and aging. This research, nearly a decade in the making, suggests that maintaining natural lithium levels in the body could help protect against Alzheimer’s-related brain changes. The findings, published in the journal Nature, could pave the way for new approaches to treatment and prevention of neurodegenerative diseases.

One of the most compelling aspects of the study is the discovery that lithium is naturally present in the body in trace amounts, much like essential nutrients such as iron or vitamin C. According to the researchers, these small quantities are not only normal but necessary for healthy cellular function. The scientists demonstrated that when lithium levels were depleted in the diets of healthy mice, the animals developed brain inflammation and signs of accelerated aging. In mice genetically predisposed to Alzheimer’s-like conditions, the absence of lithium led to a faster buildup of beta amyloid plaques and tau tangles—hallmarks of the disease—and a more rapid decline in memory.

Maintaining normal lithium levels, however, appeared to shield the mice from these degenerative changes. The study’s lead author, Dr. Bruce Yankner, emphasized that lithium might represent a common mechanism behind the brain degeneration that precedes dementia. While more research is needed to confirm these findings in humans, the results offer a promising direction for future Alzheimer’s research.

One of the more striking findings involved the role of microglia, the brain’s waste management cells. In healthy brains, microglia help clear away beta amyloid before it can accumulate. But in lithium-deficient mice, these cells lost their ability to perform this crucial task. The researchers believe that beta amyloid binds to lithium, reducing the amount available to support microglial function and creating a harmful cycle of buildup and depletion.

To test whether this cycle could be interrupted, the team administered lithium orotate—a form of lithium that does not bind to beta amyloid—to mice already showing signs of Alzheimer’s. The results were remarkable. The treated mice experienced a reduction in plaques and tangles in the brain and regained abilities in memory tasks, such as navigating mazes and recognizing new objects. In contrast, mice given a placebo showed no improvement.

Although these findings are based on animal models, they align with previous human studies suggesting a link between lithium and reduced dementia risk. A 2017 Danish study found that people with higher levels of lithium in their drinking water were less likely to be diagnosed with dementia. A 2022 study in the United Kingdom reported that individuals prescribed lithium were about half as likely to develop Alzheimer’s disease compared to a control group. These observational studies, while not definitive, support the idea that lithium might have a protective effect on the brain.

It’s important to note, however, that lithium is not without risks. In the high doses used to treat mood disorders, lithium can be toxic, particularly for older adults. Dr. Kostas Lyketsos of Johns Hopkins Medicine cautioned that even stable doses can become dangerous under certain conditions, such as dehydration. He stressed that any future use of lithium for Alzheimer’s prevention would require careful dosing and monitoring.

The researchers used modern technology to measure lithium levels in the brain and blood, something that wasn’t possible until recently due to the element’s extremely low natural concentrations. In their analysis of human brain tissue, they found consistently lower lithium levels in people with mild cognitive impairment or Alzheimer’s disease, compared to those with normal brain function. These findings were confirmed across multiple brain banks, including those at Massachusetts General Hospital, Duke University, and Washington University.

To understand how lithium loss might occur, the team investigated potential causes. They suspect that the brain’s ability to absorb lithium from the blood diminishes in the early stages of Alzheimer’s, possibly due to a mix of genetic, dietary, and environmental factors. Interestingly, many foods associated with brain health—such as leafy greens, nuts, legumes, and spices like turmeric and cumin—are also natural sources of lithium. This connection suggests that part of the benefit of a healthy diet may come from its lithium content.

I found this detail striking: the gene expression profiles of lithium-deficient mice closely resembled those of humans with Alzheimer’s disease. This parallel adds weight to the argument that lithium plays a foundational role in maintaining brain health. Still, as Dr. Yankner emphasized, mouse studies are only a first step. Human trials are necessary to determine safe and effective dosages, and to confirm whether these findings translate to people.

While the potential of lithium as a preventive tool is exciting, experts agree that it’s too early for individuals to begin supplementing on their own. The lithium doses used in the study were about 1,000 times lower than those prescribed for mood disorders and showed no signs of toxicity in mice. That’s encouraging, but not enough to recommend self-treatment. Future clinical trials will be essential to establish guidelines for safe use in humans.

As research continues, lithium’s role in brain aging and Alzheimer’s disease may become clearer. For now, this study offers a compelling new perspective on a familiar element and its unexpected importance in brain health.

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