Lithium's Potential Role in Slowing Cognitive Decline in Alzheimer’s Disease: Insights from Mouse Studies

Alzheimer's disease is characterized by progressive memory loss and cognitive deterioration, with early brain changes that remain poorly understood, making treatment development challenging. Recent research highlights a surprising candidate in the fight against this neurodegenerative disorder—lithium, a metal best known for its psychiatric use and presence in batteries. While lithium's role in mood stabilization is well established, new evidence suggests it may also be a critical factor in maintaining cognitive health.

The link between lithium and brain health gained attention after scientists observed that individuals with mild cognitive impairment—a precursor to Alzheimer’s—exhibited decreased brain lithium levels compared to healthy individuals. Further studies revealed that as the disease advances, lithium gets trapped within amyloid plaques, harmful protein accumulations that disrupt neuronal function. This trapping deprives neurons of lithium’s protective effects, potentially accelerating disease progression.

In animal models, notably genetically engineered mice prone to Alzheimer’s, researchers reduced dietary lithium by half, resulting in accelerated accumulation of amyloid-beta and tau proteins, increased brain inflammation, and impaired neuronal connections. Conversely, supplementing these mice with lithium orotate—an accessible form that can bypass plaques—prevented harmful protein buildup, reduced inflammation, and improved memory performance.

At the molecular level, the enzyme GSK3β plays a pivotal role. Lithium naturally inhibits this enzyme, preventing abnormal tau tangling and neuronal damage. When lithium levels drop, GSK3β becomes overactive, contributing to the pathological features of Alzheimer’s. Therapeutic intervention with lithium compounds appears to keep this enzyme in check, protecting neurons.

Beyond animal studies, lithium's protective effects are supported by its long-standing use in psychiatric medicine, mainly for bipolar disorder, but at doses significantly higher than natural brain levels. Interestingly, small amounts of lithium are present naturally in drinking water and diet, and emerging evidence suggests maintaining optimal levels could bolster brain resilience. Lithium orotate, a supplement form that enables lithium to reach neurons more effectively, appears promising due to its ability to avoid entrapment within amyloid plaques.

While these findings are encouraging, they are primarily based on studies in mice and postmortem human tissue examinations. Human trials are needed to confirm whether lithium supplementation can safely delay or prevent Alzheimer’s in people. The potential of lithium as a simple, accessible intervention for neuroprotection offers a new avenue in Alzheimer’s research, especially since it acts as a conductor of multiple brain processes rather than targeting a single molecule.

In conclusion, maintaining proper lithium levels might be crucial for neuronal health and could form part of a broader strategy to combat neurodegeneration. Future research will clarify whether dietary or supplemental lithium can be a safe and effective tool against Alzheimer's disease.