Lithium Isotopes Differentially Influence β-amyloid Assembly And Mitochondrial Toxicity.

 

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and is characterized by the accumulation of β-amyloid (Aβ) aggregates, oxidative stress, synaptic dysfunction, and progressive neuronal loss.

Despite decades of research, effective disease-modifying therapies remain elusive.

Lithium has emerged as a promising candidate for AD treatment due to its neuroprotective, anti-inflammatory, and antioxidant properties.

Several studies have shown that lithium can reduce Aβ production and aggregation, attenuate tau hyperphosphorylation through GSK-3β inhibition, improve mitochondrial function, and enhance neuronal survival. Epidemiological and preclinical evidence further suggests that chronic lithium exposure may be associated with a reduced risk of dementia and slower cognitive decline.

Naturally occurring lithium consists of two stable isotopes, Lithium-6 (⁶Li) and Lithium-7 (7Li), which differ in atomic mass and nuclear spin.

While lithium’s biological activity has traditionally been attributed to its chemical properties, emerging evidence suggests that isotope-specific nuclear effects may influence molecular interactions and cellular responses.

Objective: To investigate whether ⁶Li and 7Li differentially modulate Aβ aggregation, aggregate structure, cellular interactions, and mitochondrial function, thereby uncovering a potential isotope-dependent regulation of amyloid pathogenicity and neurotoxicity.