CAMBRIDGE, August 6, 2025 – Published this week in Nature, a Harvard Medical School study reveals that naturally occurring lithium, a trace mineral vital for brain health, is severely depleted in the early stages of Alzheimer’s disease and may be a key driver of its progression.
By analysing post-mortem brain tissue, researchers found that lithium concentrations in the hippocampus – the brain’s memory centre – were significantly lower in people with mild cognitive impairment and Alzheimer’s than in healthy individuals. They believe toxic amyloid-β plaques, a hallmark of the disease, physically trap lithium, preventing it from carrying out its protective role in nerve cells.
To investigate the consequences, the team used lab models mimicking Alzheimer’s pathology. In these experiments, lithium depletion accelerated brain changes linked to memory loss, including the accumulation of amyloid and tau proteins, the breakdown of synapses, and the deterioration of myelin sheaths that protect nerve fibres. These changes mirror those seen in patients and are believed to directly contribute to cognitive decline.
The breakthrough came when the scientists administered lithium orotate, a form of lithium that can bypass plaque sequestration and reach brain tissue. In the experiments, the compound not only halted further brain damage but reversed existing signs of disease. Mice given the treatment regained memory performance comparable to much younger, healthy animals.
Although lithium has long been prescribed in higher doses to treat bipolar disorder, lithium orotate is a low-dose dietary supplement available over the counter in some countries. The researchers caution against self-medication, warning that dosage, delivery, and safety for long-term use in Alzheimer’s patients remain untested in humans.
Lead investigators say the results point to an entirely new line of attack against Alzheimer’s – one based on restoring essential brain chemistry rather than only targeting protein build-up. Experts not involved in the research have described the findings as “very exciting” and potentially transformative, while stressing the urgent need for rigorous clinical trials to determine whether the benefits seen in the laboratory can be replicated in people.