Lithium: A New Clue in Early Alzheimer’s Disease

110104 김라온

Sources Nature , “Lithium deficiency and the onset of Alzhei mer’s disease” ScienceTimes, “알츠하이머병 치료의 새로운 전환점: 리튬의 재발견”

A recent paper published in Nature has highlighted lithium as a potential key to understanding the early development of Alzheimer’s disease. The researchers reported that lithium, long recognized as a prescribed drug at high doses, is in fact present in the brain at low, physiological levels that appear to be essential for maintaining neuronal health.

By analyzing human brain tissue, they found that individuals with mild cognitive impairment or Alzheimer’s disease had markedly lower levels of lithium in the prefrontal cortex. Another important finding was that amyloid-β plaques, the protein aggregates characteristic of Alzheimer’s, actually sequester lithium, trapping it inside the plaques and reducing its availability to surrounding tissue.

In a series of mouse experiments, the team demonstrated that a lithium-deficient diet could induce Alzheimer-like pathology. Mice deprived of lithium displayed increased amyloid- deposition, greater accumulation of β hyperphosphorylated tau, heightened neuroinflammation, damage to synapses and myelin, and measurable cognitive deficits such as impaired memory performance. To test whether restoring lithium could reverse or prevent these effects, the researchers supplemented animals with lithium orotate, a salt form of lithium that appeared less likely to bind to amyloid plaques.

This intervention successfully prevented memory loss and pathological brain changes in the mice. In contrast, the more traditional lithium carbonate, which is prone to plaque binding, proved less effective. On a mechanistic level, the pathological consequences of lithium deficiency were linked to activation of kinases such as GSK3 and to gene expression changes across multiple brain β cell types that closely resembled those seen in human Alzheimer’s tissue.

Together, these results present lithium not merely as a psychiatric drug but as a natural element with a fundamental physiological role in the brain. The findings suggest that depletion of available lithium may actively contribute to the onset and progression of Alzheimer’s disease, and that maintaining lithium homeostasis could be crucial in protecting cognitive function.