New research finds lithium depleted in the brains of Alzheimer’s patients
Groundbreaking research finds that depletion of brain lithium occurs in people with mild cognitive impairment, accelerating the path to Alzheimer’s disease. The researchers reported that mice with no lithium in their diet developed memory loss and brain changes similar to Alzheimer’s disease. Replacing low-dose lithium reversed pathological changes and memory loss, offering a new method of preventing and treating the disease.
What is lithium?
Alzheimer’s disease has long baffled scientists and those affected by the disease. While researchers have made strides in understanding the hallmarks of the disease – like amyloid plaques and tau tangles – there’s still no cure, and current treatments offer limited help. But a groundbreaking new study published in Nature in August 2025 offers a surprising and hopeful insight: the brain’s lithium levels may play a critical role in the development and progression of Alzheimer’s.
Lithium is a trace mineral, a white alkali metal, naturally found in rocks and mineral spring water. In a medical context, most people associate lithium with treatment for bipolar disorder. But its effects are also important for brain health. Lithium can help shield brain neurons from stress, promote the growth of new neurons, and regulate neurotransmitters.
Earlier studies reported that trace levels of lithium in drinking water were related to lower rates of dementia and reduced deaths from Alzheimer’s disease. (See our page on lithium for Alzheimer’s disease prevention for more details.)
The recent study from researchers at Harvard University greatly expands our understanding of lithium and brain health, bringing it to the forefront of initiatives to prevent and treat Alzheimer’s disease
Low lithium levels related to early Alzheimer’s disease
Researchers led by Bruce A. Yankner, MD, PhD (Professor of Genetics and Neurology at Harvard Medical School) discovered that lithium levels are significantly lower in the brains of people with Alzheimer’s or mild cognitive impairment compared to healthy individuals. The changes didn’t show up in blood tests, suggesting that the effect was specifically related to the deficiency of lithium in the brain regions like the prefrontal cortex.
The study also found that lithium accumulates within amyloid plaques, the clumps of protein fragments that accumulate in the brains of individuals with Alzheimer’s disease. The new data suggest that the plaques may sequester this critical element, reducing its availability elsewhere in the brain.
Experiments in mice mirror human findings
Following the human studies, the research team studied mice fed a lithium deficient diet. Their brains developed the hallmarks of Alzheimer’s disease or dementia: increased amyloid plaques, tau pathology, myelin loss, neuroinflammation, synaptic damage, and memory impairments. Conversely, restoring lithium reversed many of these Alzheimer’s like changes.
Lithium carbonate is known for treating depression and bipolar disease in high doses, as well as being studied for the prevention and treatment of diseases like Alzheimer’s. Unfortunately, it has a narrow therapeutic range and serious side effects – including toxic impacts on the thyroid and kidneys.
The researchers instead chose lithium orotate for the mouse study. Unlike traditional lithium carbonate, the orotate type was not trapped by plaques, reached healthier brain regions more effectively, and reversed pathology without detectable toxicity. It is effective in low doses.
Understanding why lithium may prevent Alzheimer’s
A central part of the story is GSK 3β, an enzyme implicated in Alzheimer’s involved in the formation of plaques and tangles. Lithium normally inhibits GSK 3β, helping prevent tau phosphorylation, amyloid accumulation, and other damage. Without enough lithium, GSK‑3β goes unchecked, accelerating disease processes. Restoring physiological lithium levels helps keep it in balance.
This makes lithium not just a bystander, but potentially a gatekeeper for brain health. By restoring lithium levels in the brin, especially in early stages, we may be able to slow, or even prevent, the neurodegeneration that leads to Alzheimer’s.
Lithium therapy offers hope for the future
Lithium could be a gamechanger for the prevention and treatment of Alzheimer’s disease. In a commentary on the study, neuroscientist Ashley I. Bush said “Lithium in the brain has been found to protect against cognitive decline. Restoring lost lithium could be a new angle from which to tackle Alzheimer’s disease.”
Lithium is inexpensive, accessible, and—when carefully administered—safe. Lithium orotate in particular, shows promise for preventive strategies, and could be especially helpful in low-resource communities where access to high-cost therapies is limited.
The need for effective therapies is crucial. Current Alzheimer’s treatments offer modest benefits and carry risks, highlighting the need for alternatives. While the results of the Harvard study are compelling, human trials are essential before considering any clinical use. This will take time and resources.
The Parsemus Foundation fully supports more investment in studies of lithium orotate for the prevention and treatment of Alzheimer’s disease. We have provided funding for a study conducted by researchers at the University of Saskatchewan using lithium orotate in a mouse model of Alzheimer’s.
For more news on preventing dementia and Alzheimer’s disease, see our related blog posts and pages.
