Lithium: the protective cation singled out by Alzheimer's disease

Lithium is a mood stabilizer that is most prescribed in psychiatry for managing mental disorders. Many findings indicate that lithium is also neuroprotective in various neurodegenerative diseases. In particular, lithium has been of great interest as an affordable but still effective treatment for Alzheimer's disease (AD), due to its diverse neuroprotective actions and mechanistic overlap with key AD pathways, such as A production and tau modification. While the multifaceted activities may result from lithium's inhibitory action on two key enzymes, glycogen synthase kinase-3 beta (GSK-3) and inositol monophosphatase (IMPase), recent findings suggest that selective lithium depletion in neurons mediated by amyloid deposits may be a key pathological trigger in AD and supplementation with lithium orotate, a lithium salt with reduced amyloid binding, may even reverse brain damage and prevent cognitive decline. In this study, we review the neuroprotective properties of lithium, its known mechanisms of action, and discuss its therapeutic potential in AD, a topic that has been debated for decades. [BMB Reports 2026; 59(10): 456-465].