A Surprising Link Between Lithium and Alzheimer’s

Recent research is shedding new light on the complex relationship between lithium levels in the brain and the onset of Alzheimer's disease (AD) and dementia. Scientists have long known about the accumulation of amyloid plaques and tau tangles in the brains of those afflicted with AD, but how these proteins interact with metal ions in the brain has remained mostly a mystery.

The Metal Factor

Led by Dr. Bruce Yankner from Harvard Medical School, a pioneering team of researchers set out to decipher how metal ions, such as lithium, could influence brain function and cognitive decline. They specifically focused on the differences in metal levels among individuals with mild cognitive impairment (MCI)—often a precursor to AD—and those diagnosed with AD.

Startling Findings on Lithium Levels

Analyzing post-mortem brain samples, the team quantified 27 different metals across various brain regions. Their findings were striking: there was a marked reduction in lithium levels within the prefrontal cortex of patients with MCI and AD. This area of the brain is crucial for memory and decision-making, and the decline in lithium could potentially have significant implications for cognitive functions.

Lithium’s Role in Amyloid Plaques

Intriguingly, the research revealed that lithium appears to accumulate within amyloid plaques, with concentrations increasing from MCI to AD. Meanwhile, levels of lithium in plaque-free regions plummeted in those with AD, suggesting that amyloid plaques may actively sequester lithium.

Impacts on AD Pathogenesis in Mouse Models

To understand how lithium depletion influenced Alzheimer’s pathology, the researchers conducted experiments on mouse models. Those on a low-lithium diet exhibited increased amyloid plaques and tau tangles, resulting in notable declines in learning and memory. This depletion not only affected plaque formation but also altered gene expression in critical brain cells.

Exploring Lithium Supplements for Treatment

The researchers then investigated whether supplementing with lithium could alter the AD landscape. While lithium carbonate, commonly prescribed for mood stabilization, showed minimal effects, lithium orotate—a more organic form—demonstrated significant promise. In trials, it notably reduced amyloid burden and tau accumulation, while also improving synaptic function and memory in AD-affected mice.

A Glimmer of Hope for Aging Brains

Not only did lithium orotate prove effective in AD models, but it also safeguarded against cognitive decline in aging mice without AD pathology. Over extended periods, it showed no signs of toxicity, making it an intriguing candidate for further studies.

Looking Ahead: Clinical Trials on the Horizon

Dr. Yankner highlights the groundbreaking revelation that lithium deficiency may contribute to the onset of Alzheimer’s, paving the way for innovative therapeutic strategies. However, he emphasizes the necessity for clinical trials to establish effective and safe dosage in humans, with plans for such a study already in the works.