Sy Boles

Harvard Staff Writer

January 27, 2026 6 min read

Harvard file photo

Part of the Profiles of Progress series

Bruce Yankner has had a busy couple of months.

In August, his team published groundbreaking research showing that lithium is a natural, biologically important element in the brain that has the potential to prevent or even reverse Alzheimer’s disease. The findings mark a potentially major leap in understanding a disease that affects more than 50 million people worldwide, and that so far has proved frustratingly difficult to treat.

Ever since, his inbox and phone have been flooded with messages from people suffering from the condition, or their loved ones, looking for advice or support.

“I try to get back to everybody who contacts me,” said Yankner, a professor of genetics and neurology at Harvard Medical School and the co-director of the Paul F. Glenn Center for the Biology of Aging. “I try to provide hope.”

“I try to provide hope.”
Bruce Yankner

Yankner’s NIH- and foundation-funded research showed that lithium occurs naturally in the brain and maintains the normal function of major brain cell types — and that lithium depletion is one of the earliest changes in Alzheimer’s disease. Additionally, the work demonstrated that reduced lithium levels occurred when amyloid plaques — accumulations of aggregated protein in Alzheimer’s — bind the metal, further reducing the amount available to support normal brain function. When his team, which included research associate Liviu Aron and postdoctoral fellows Ngian Zhen Kai and Chenxi Qiu, reproduced this level of lithium depletion in the mouse brain, it dramatically accelerated the disease and led to memory loss.

Lastly, the study suggested that a novel lithium compound, lithium orotate, which was selected for reducing binding to amyloid, could prevent and reverse Alzheimer’s pathology and memory loss in mouse models.

Process-oriented and measured, even Yankner admits the research is exciting. But when people ask him if they or their loved ones should take lithium supplements, he tells them he hopes clinical trials will soon determine whether the treatment is safe and effective in people, and suggests they consult with their physician.

“People who have loved ones with Alzheimer’s understandably have difficulty waiting for the results of clinical trials, which by their nature, take a long time,” he said. “But our method of going from the laboratory to the clinical trial has been validated many times. In this case, we are lucky to be able to move forward rapidly because of enlightened philanthropy.”

“Our method of going from the laboratory to the clinical trial has been validated many times. In this case, we are lucky to be able to move forward rapidly because of enlightened philanthropy.”
Bruce Yankner

Yankner, who was a long-distance runner for much of his adulthood, knows firsthand that rigorous scientific research is a marathon, not a sprint.

After completing undergraduate study at Princeton University and earning an M.D./Ph.D. at Stanford University, Yankner came to Massachusetts General Hospital for a residency in neurology. There, he got to wondering what oncogenes, which cause cancer by pushing cells to divide, do to neurons, which can’t divide. He hypothesized that instead of causing uncontrolled growth, oncogenes in neurons might cause cell damage or degeneration, contributing to Alzheimer’s disease or other neurodegenerative disorders.

In what was a technical feat for the ’80s, Yankner introduced a variety of foreign genes into neuronal cells to test the hypothesis.

“As sort of an afterthought, I introduced the amyloid precursor protein gene that gives rise to amyloid protein,” he explained. “It was just one of the many genes I was testing.”

At the time, amyloid was thought to be an inert byproduct of Alzheimer’s disease. But Yankner found that neurons that overexpress the amyloid precursor gene had begun to die. He had discovered that far from being a harmless byproduct, amyloid was in fact toxic to neurons, suggesting that it might play a causal role in Alzheimer’s. That finding, first made in the early 1990s, together with the genetics of the disease, has shaped decades of Alzheimer’s research and is foundational to amyloid-targeting drugs such as lecanemab and donanemab, which were recently approved by the FDA.

Yankner’s work has extended into other areas since then, including the basic science of aging and gene regulation in the brain, Parkinson’s disease, Down’s syndrome, and psychiatric disease. But he was always bothered by a missing link in what came to be known as the amyloid hypothesis of Alzheimer’s disease: Some people can have brains riddled with amyloid plaques and have relatively intact cognition, while others who have similar amounts of amyloid are severely impaired.

The recent findings provide a potential explanation. By showing that amyloid binds to and neutralizes lithium, and that aging individuals can vary in their baseline lithium levels, Yankner’s team may be starting to understand the imperfect correlation between amyloid and disease symptoms.

It was a finding 10 years in the making. It required overcoming several technological hurdles, such as the ability to detect very low levels of a metal not previously thought to exist naturally in the body; the development of mouse models that could demonstrate the impact of a loss of lithium in the brain; and the creation of a new screening platform to test a series of lithium compounds to find those that can evade lithium binding.

But now, “at a point where we feel there’s significant, rapid progress to be made,” he worries it might be delayed.

“Hopefully, in the not-too-distant future, we will have some objective data about the efficacy and safety of lithium orotate.”
Bruce Yankner

A U.S. District Court in September struck down the Trump Administration’s cancelation of $2.2 billion in research funding to Harvard, restoring critical grants supporting lifesaving research. But with two major federal grants ending in the near future, Yankner isn’t sure how forthcoming new rounds of funding might be.

Still, he is collaborating with researchers at Mass General and Brigham and Women’s Hospital on a clinical trial of lithium orotate, which is expected to begin this spring.

“Hopefully, in the not-too-distant future, we will have some objective data about the efficacy and safety of lithium orotate,” he said. “Many people are waiting for this.”