Brain Lithium Drop Fuels Alzheimer’s Onset
New Study Links Deficiency to Early Disease Progression, Offers Hope for Treatment
A groundbreaking study reveals that dwindling lithium levels in the brain may be an early trigger for Alzheimer’s disease, accelerating its progression. Research in mice suggests that replenishing these levels, particularly with low-dose lithium orotate, could shield against memory loss and brain damage.
Unveiling Lithium’s Crucial Role
Scientists have discovered that naturally occurring lithium in the brain plays a vital protective role against cognitive decline. The research indicates that a reduction in this internal lithium supply contributes to the initial pathological changes seen in Alzheimer’s disease. Conversely, restoring these levels in animal models showed promise in preventing brain damage and memory impairments, highlighting a potential preventative and therapeutic avenue.
Lithium Levels Decline in Alzheimer’s Brains
The investigation analyzed lithium concentrations in human brain and blood samples from individuals with varying cognitive statuses. Employing highly sensitive mass spectrometry, researchers measured lithium levels in brain regions such as the cortex and cerebellum, as well as in blood serum. They observed significantly lower lithium concentrations in the brains of individuals experiencing mild cognitive impairment and Alzheimer’s disease compared to those with no cognitive issues.
This depletion was specifically noted in the prefrontal cortex, an area profoundly impacted by Alzheimer’s. Intriguingly, lithium was found to be highly concentrated within amyloid-β plaques, suggesting these plaques may sequester the mineral, thereby reducing its availability in surrounding brain tissue.
Mouse Models Show Promising Results
Experiments involving mouse models explored the impact of lithium deficiency and supplementation. Mice fed a diet severely lacking in lithium exhibited reduced brain lithium levels, a pattern amplified in strains predisposed to Alzheimer’s. These mice showed increased amyloid-β buildup, tau pathology, synapse and myelin loss, and neuroinflammation, alongside cognitive deficits.
In contrast, lithium supplementation, particularly through lithium orotate, successfully restored brain lithium levels and mitigated many Alzheimer’s-related changes, including plaque formation and inflammation. The study indicated that lithium orotate was more effective than lithium carbonate at enhancing lithium in non-plaque brain tissue, and importantly, showed no toxicity at the low doses administered. This is a significant finding, as standard lithium therapies can have toxicity concerns.
Mechanism and Future Directions
The research suggests that lithium deficiency activates the enzyme GSK3β, which in turn promotes neurodegeneration. This effect was reversed in mice treated with GSK3β inhibitors. The findings imply that early neurodegenerative changes might be driven by lithium deficiency, positioning it as a key target for Alzheimer’s prevention and treatment.
The study’s authors propose that past human trials may have been hampered by issues with lithium formulations, such as high amyloid binding with certain salts. Restoring physiological lithium levels, especially with the more brain-accessible lithium orotate, presents a promising strategy to combat cognitive decline and Alzheimer’s pathology.
Globally, over 55 million people are living with dementia, and Alzheimer’s disease is the most common cause, projected to rise as populations age (World Health Organization, 2023). This research offers a vital new perspective on understanding and potentially intervening in the early stages of this devastating disease.
Journal reference: Aron, L., Ngian, Z.K., Qiu, C., Choi, J., Liang, M., Drake, D.M., Hamplova, S.E., Lacey, E.K., Roche, P., Yuan, M., Hazaveh, S.S., Lee, E.A., Bennett, D.A., Yankner, B.A. Nature (2025). https://www.nature.com/articles/s41586-025-09335-x
