Longevity & AgingBrain Lithium Deficiency Emerges as an Early Driver of Alzheimer's Disease
Researchers at Harvard Medical School measured 27 metals in human brain tissue and found lithium was uniquely depleted in the prefrontal cortex of people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Amyloid plaques were shown to sequester lithium, reducing its bioavailability. In mouse models, cutting dietary lithium by ~50% in the brain accelerated amyloid deposition, phospho-tau accumulation, neuroinflammation, synapse loss, and cognitive decline. These effects were mediated partly through GSK3β activation. Single-nucleus RNA sequencing revealed that lithium deficiency produces transcriptomic changes overlapping with human AD. Crucially, replacing lithium using lithium orotate—a salt with low amyloid binding—prevented pathology and memory loss in both AD mouse models and aging wild-type mice.
