Repeated inability to remember names or facts, especially newly encountered ones, is often an early sign of Alzheimer's disease (AD), a disorder first described by a German physician, Alois Alzheimer, in 1906.

It is estimated that more than 400 million people suffer from AD worldwide, and the number of cases is expected to continue to surge as global populations age. Alzheimer's is the most common form of dementia, responsible for 50 to 70 percent of dementia diagnoses.

The cause of Alzheimer's, a neurodegenerative disease, remains elusive. Despite decades of effort to pinpoint genetic and environmental causes that could be definitively linked to AD, no clear pathway to either a cure or effective treatment has emerged.

Lithium is a key component of normal brain functioning. A deficiency of it accelerated the formation of the tangled amyloid-beta plaques which scientists have long believed are responsible for the brain disruption seen in AD.

The good news is that researchers at Harvard University may have found an exciting and important clue to the early spark that comes to erode the minds and memories of AD patients — lithium depletion.

“The idea that lithium deficiency could be a cause of Alzheimer's disease is new and suggests a different therapeutic approach,” the study's senior author and Harvard Medical School professor, Bruce Yankner, said.

Working with mouse models and human brain tissue taken postmortem, the researchers confirmed that lithium is a key component of normal brain functioning. When lithium was depleted, the study showed the formation of the tangled structures scientists have long suggested are responsible for the brain disruption seen in AD, amyloid-beta plaques, accelerated.

The researchers also found that lithium depletion activated microglia, specialized brain inflammatory cells, impairing their ability to degrade amyloid and interrupting brain connections. Lithium depletion also degraded the protective myelin sheath that covers brain cells, and in so doing, produced the cognitive decline, memory loss and, ultimately, dementia that are the defining features of AD.

Physicians, for many years, have prescribed lithium, usually in the form of oral tablets of lithium carbonate, to stabilize mood, particularly for patients with bipolar disorder, schizophrenia and major depression.

Many studies have shown that these lithium-treated patients have a significantly lower risk of AD later in life, so why were the few clinical trials with lithium carbonate for AD disappointing?

The key reasons are that the clinical standard, lithium carbonate, that is often prescribed to people diagnosed with bipolar disorder, can be toxic to aging people at the high doses normally used. And, in addition, the new research showed that the amyloid beta tangles trap the lithium carbonate compounds before they can work.

After screening other lithium compounds, the Harvard team found that lithium orotate, sometimes marketed as a dietary supplement, was able to bypass amyloid beta plaques and therefore, even at low doses, offer protection against Alzheimer's.

Lithium depletion activated microglia, impairing their ability to degrade amyloid, interrupting brain connections. It also degraded the protective myelin sheath that covers brain cells, producing cognitive decline.

Whether these results, conducted in mice, apply to the treatment of Alzheimer's in humans, remains to be determined. If future research confirms these findings, routine blood tests may one day offer a way to identify individuals at risk for Alzheimer's who would benefit from treatment to prevent or delay AD onset.

Yankner, a professor of genetics and neurology in the Blavatnik Institute at Harvard Medical School, hopes, “…that lithium will do something more fundamental than anti-amyloid or anti-tau therapies, not just lessening but reversing cognitive decline and improving patients' lives.”

The study is published in Nature.