A Nature paper from Harvard Medical School reports that naturally occurring lithium in the brain appears to protect against Alzheimer’s disease and that its depletion may help trigger the condition. Analysing post-mortem tissue from 285 people, the researchers found lithium concentrations in the pre-frontal cortex were roughly one-third lower in patients with mild cognitive impairment and full-blown Alzheimer’s than in cognitively healthy donors. Much of the residual metal was trapped inside amyloid-β plaques, further reducing its bio-availability. Replicating the deficiency in mice, the team cut dietary lithium by 92 per cent. The animals developed heavier amyloid and phospho-tau pathology, activated microglia, lost synapses and performed poorly in memory tasks. Supplementation with lithium orotate—a lightly ionised organic salt—at physiologic doses of 4.3 µEq l⁻¹ reversed cognitive deficits and shrank plaque burden by up to 70 per cent, whereas equivalently dosed lithium carbonate had little effect because it bound strongly to amyloid deposits. Lead author Bruce Yankner said the data point to lithium homeostasis as an early, treatable driver of Alzheimer’s. Experts who were not involved welcomed the mechanistic insight but cautioned that larger safety studies are required; conventional lithium therapy for bipolar disorder is given at levels roughly 1,000-fold higher and can harm kidneys and thyroids. The Harvard group aims to launch clinical trials to test whether low-dose lithium orotate can safely delay or prevent the disease in people at risk.