Lithium and Alzheimer’s: In a breakthrough nearly a decade in the making, scientists at Harvard Medical School have uncovered compelling evidence that the trace metal lithium, best known as a psychiatric drug, may play a crucial role in brain health and ageing, potentially offering a new path to understanding and treating Alzheimer’s disease.
In a study published in Nature, researchers from Harvard and Rush University reported that lithium, naturally present in the human body in tiny amounts, is essential for normal cellular function, similar to vital nutrients like vitamin C or iron. Their experiments showed that reducing lithium in the diets of mice accelerated signs of brain ageing and Alzheimer’s-like damage.
“This is a potential candidate for a common mechanism leading to the multisystem degeneration of the brain that precedes dementia,” said Dr. Bruce Yankner, senior author of the study and professor of genetics at Harvard. He added that while more research is needed, the findings could unify decades of puzzling Alzheimer’s research.
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Researchers fed healthy mice a lithium-depleted diet, which led to increased inflammation and brain changes resembling those found in Alzheimer’s patients. In mice that were genetically modified to develop Alzheimer’s, low lithium levels made the buildup of beta-amyloid plaques and tau tangles, which are key features of the disease, even worse.
Conversely, maintaining normal lithium levels helped protect the brain from these degenerative changes. Mice that were given lithium orotate, a special compound that doesn’t attach to amyloid, performed better in thinking tasks, had less plaque buildup, and kept their memory functions stronger.
The research team found that beta-amyloid plaques bind to lithium, trapping it and starving nearby brain cells of this essential element. This disrupts microglia, the immune cells responsible for clearing harmful proteins from the brain, and may trigger a downward spiral of plaque buildup and inflammation.
Tests on human brain tissue confirmed the connection. Alzheimer’s patients had consistently lower lithium levels in their brains compared to those without memory impairment. This pattern held across multiple brain banks, including those at Massachusetts General Hospital, Duke, and Washington University.
Yankner emphasised that the amounts of lithium used in the study were about 1,000 times lower than the doses used for psychiatric treatment, and mice showed no signs of toxicity. However, he cautioned against self-medicating, stressing that human trials are needed.
Lithium’s role in brain health has been hinted at before. Studies in Denmark and the UK have found that populations exposed to higher levels of lithium in drinking water had lower rates of dementia. But until now, the mineral’s role in normal brain physiology was poorly understood due to the tiny concentrations present in the body.
