In a study culminating nearly a decade of research, scientists at Harvard Medical School have identified the metal lithium as a potentially crucial factor in understanding Alzheimer’s disease and brain aging. Published Wednesday in the journal Nature, the findings suggest that lithium, widely known as a medication for mood disorders, is also a naturally occurring and essential element for normal cellular function, much like a vitamin.
The research, conducted in collaboration with Rush University, revealed that lithium plays a critical role in maintaining brain health. In a series of experiments, researchers found that when healthy mice were fed a diet depleted of lithium, their brains developed inflammation and changes associated with accelerated aging.
For mice genetically engineered to develop Alzheimer’s-like pathology, a low-lithium diet accelerated the buildup of amyloid plaques and tau tangles—the hallmarks of the disease—and hastened memory loss. Conversely, maintaining normal lithium levels throughout the aging process protected the mice from these degenerative brain changes.
The study provides a unifying theory for the disease’s progression. The researchers discovered that beta-amyloid plaques, the sticky protein deposits in Alzheimer’s brains, bind to and trap lithium. This depletes the lithium available to nearby brain cells, including microglia, which are the brain’s immune cells responsible for clearing away waste. When microglia are starved of lithium, their ability to remove beta-amyloid is impaired, creating a downward spiral where plaque accumulation further reduces available lithium, crippling the brain’s defense mechanisms.
The team also identified a specific compound, lithium orotate, that does not bind to amyloid plaques. When administered to mice showing signs of Alzheimer’s, this compound reversed the disease’s progression. It reduced both plaques and tangles in the brain’s memory centers and restored cognitive function, enabling the mice to navigate mazes and recognize new objects successfully.
These findings were corroborated by an analysis of human brain tissue. Scientists measured trace levels of 27 metals in samples from the Rush University brain bank and found that lithium levels were consistently lower in patients with Alzheimer’s or mild cognitive impairment compared to those with normal brain function. This observation held true across samples from several other brain banks.
This research builds on earlier studies that hinted at lithium’s protective role. A 2017 Danish study found that populations with higher levels of naturally occurring lithium in their drinking water had lower rates of dementia, and a 2022 UK study noted that patients prescribed lithium were less likely to be diagnosed with Alzheimer’s.
Despite the promising results, the study’s lead author, Dr. Bruce Yankner, a professor of genetics at Harvard Medical School, strongly cautioned against self-medicating with lithium supplements. “A mouse is not a human,” Yankner stated, emphasizing the need for human trials to replicate the findings and establish a safe, effective dose. The amounts of lithium used in the mouse experiments were about 1,000 times lower than the therapeutic doses prescribed for bipolar disorder, and tests on the mice showed no signs of toxicity at these low levels.
The research also offers a potential explanation for the known benefits of certain diets. Major dietary sources of lithium include leafy green vegetables, nuts, and legumes—foods that are cornerstones of diets proven to reduce dementia risk. The study suggests that the lithium content of these foods may be a previously unappreciated reason for their brain-healthy effects.
