The effects of Lithium on Beta-amyloid deposition and tau phosphorylation: A systematic review

Lithium demonstrates neuroprotective and neurotrophic effects, and preclinical studies indicate lithium reduces intracerebral amyloid deposition and tau phosphorylation. This systematic review evaluates lithium's effects on beta-amyloid, tau, and cognitive deficits in major neurocognitive disorders.

A systematic review of primary research was conducted using Embase, PsycInfo, MEDLINE, and PubMed databases from inception to September 2024, following PRISMA criteria. Animal and adult human studies evaluating lithium monotherapy's effects on Alzheimer's Disease (AD) were included.

Long-term low-dose lithium treatment demonstrates inconsistent effects on lowering intracerebral amyloid deposition and reversing AD-related cognitive deficits in preclinical and clinical trials. Lithium was reported to slows amyloid plaque formation in pre-plaque stages through increasing heat shock proteins and suppressing protein synthesis in preclinical trials. Intracerebral lithium reduced phosphorylated tau through promoting tau ubiquitination and inhibiting CDK5 signalling in preclinical trials.

A comprehensive animal model that accurately represents human AD symptoms and progression, as well as more clinical trials are needed. Several included studies utilize peripheral lithium administration, which complicates assessment of effective intracerebral concentrations.

Lithium potentially reduces intracerebral amyloid deposition and tau phosphorylation in AD animal models and may reverse associated cognitive deficits. Further research should seek to replicate similar findings in larger samples and explore lithium's optimal dosage range in promoting intracerebral amyloid clearance.