Lithium deficiency and the onset of Alzheimer's disease.

ABSTRACT: The earliest molecular changes in Alzheimer's disease (AD) are poorly understood^1-5. Here we show that endogenous lithium (Li) is dynamically regulated in the brain and contributes to cognitive preservation during ageing. Of the metals we analysed, Li was the only one that was significantly reduced in the brain in individuals with mild cognitive impairment (MCI), a precursor to AD. Li bioavailability was further reduced in AD by amyloid sequestration. We explored the role of endogenous Li in the brain by depleting it from the diet of wild-type and AD mouse models. Reducing endogenous cortical Li by approximately 50% markedly increased the deposition of amyloid-β and the accumulation of phospho-tau, and led to pro-inflammatory microglial activation, the loss of synapses, axons an

SUBMITTER: Aron L 

PROVIDER: S-EPMC12443616 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature