Alzheimer’s Disease: Could Lithium Deficiency Be a Key Cause?

Origins of the Amyloid Cascade Hypothesis and Alternative Research

The condition takes its name from Dr. Alois Alzheimer, who in 1906 identified abnormal tissue changes in the brain of a woman who died following a severe and unusual illness characterized by memory loss, language problems, and unpredictable behavior. Upon examining her brain, Dr. Alzheimer discovered abnormal clumps, now known as amyloid-beta plaques, alongside tangles of tau protein fibers. Over subsequent decades, epidemiological studies established multiple underlying risk factors for the condition, including hypertension, smoking, alcohol use, diabetes, poor diet, physical inactivity, air pollution, low educational attainment, and stress. Despite extensive investigation into these risk factors, therapeutic trials targeting amyloid-beta have faced significant limitations. These challenges have prompted researchers to question whether amyloid-beta plays as central a role in neurodegeneration as previously assumed. Citing economist John Maynard Keynes, researchers note that the primary difficulty in scientific advancement often lies not in developing new ideas, but in escaping old ones. Consequently, investigators are exploring biological mechanisms outside the traditional amyloid cascade framework to understand what triggers the disease in its earliest stages.

The Neuroprotective Role of Endogenous Lithium

Researchers are now examining the potential role of endogenous lithium in the onset of Alzheimer’s disease. While lithium compounds have been utilized for decades to treat bipolar disorder and are recognized for cognitive and physiological benefits, recent work highlights its broader neuroprotective potential. In low doses, lithium helps maintain mitochondrial function, supports axonal regeneration, and facilitates remyelination. The litio es “secuestrado” por placas de amiloide-β The 2024 study by Monique Patricio Singulani and colleagues demonstrates that lithium treatment correlates with a lower accumulation of beta-amiloide plaques and neurofibrillary tangles, alongside greater preservation of dopaminergic neurons. Conversely, studies show that endogenous lithium levels drop in the prefrontal cortex of individuals experiencing mild cognitive impairment and Alzheimer’s disease because the element becomes trapped within amyloid-beta deposits. This deficiency creates a biological cascade that worsens tau and amyloid accumulation while accelerating cognitive decline. Experimental diets deficient in lithium have also been shown to exacerbate amyloid pathology in study models.

Global Impact and Awareness Initiatives

To highlight the broader societal impact of the condition, September 21 is observed annually as the day of Alzheimer. The commemorative date aims to raise public awareness, promote social understanding, and advocate for increased research funding, medical resources, and family support systems. The condition places a disproportionate burden on women, who experience higher rates of disability and mortality while also shouldering approximately 70 percent of caregiving hours. Although the emerging focus on lithium deficiency offers a promising avenue for future prevention and treatment strategies, researchers emphasize that extensive clinical investigation remains necessary before these insights translate into established medical therapies.