Carbon beam transmission therapy reverses iron deposits and microglia-driven neuroinflammation and induces cognitive improvement in an Alzheimer’s disease mouse model.

Abstract

Background Insoluble iron deposits often exist as iron oxide nanoparticles in protein aggregates, impaired ferritin, or activated microglia, and have been implicated as a major culprit of neuroinflammation in Alzheimer’s disease. However, no crucial evidence has been reported to support the therapeutic effects of current iron chelators on the deposition of various molecular forms of insoluble iron. Methods We investigated the therapeutic effect of carbon ion stimulation (CIS) via the use of a transmission beam on insoluble iron deposits and the associated biological response in AD mouse brains. Results Compared no treatment, CIS dose-dependently induced a 33–60% reduction in the amount of ferrous-containing iron species and associated inclusion bodies in the brains of AD mice. CIS induced considerable neuroinflammation downregulation and conversely anti-inflammatory upregulation, which was associated with improved memory and enhanced hippocampal neurogenesis. Conclusions In conclusion, our results suggest that the effective degradation of insoluble iron deposits in combination with pathogenic inclusion bodies plays a role in promoting AD-modifying properties and offers a potential carbon ion treatment option for AD.