Photo-oxygenation by a biocompatible catalyst reduces amyloid-β levels in Alzheimer's disease mice

Amyloid formation and the deposition of the amyloid-beta peptide are hallmarks of Alzheimer's disease pathogenesis. Immunotherapies using anti-amyloid-beta antibodies have been highlighted as a promising approach for the prevention and treatment of Alzheimer's disease by enhancing microglial clearance of amyloid-beta peptide. However, the efficiency of antibody delivery into the brain is limited, and therefore an alternative strategy to facilitate the clearance of brain amyloid is needed. We previously developed an artificial photo-oxygenation system using a low molecular weight catalytic compound. The photocatalyst specifically attached oxygen atoms to amyloids upon irradiation with light, and successfully reduced the neurotoxicity of aggregated amyloid-beta via inhibition of amyloid formation. However, the therapeutic effect and mode of actions of the photo-oxygenation system in vivo remained unclear. In this study, we demonstrate that photo-oxygenation facilitates the clearance of aggregated amyloid-beta from the brains of living Alzheimer's disease model mice, and enhances the microglial degradation of amyloid-beta peptide. These results suggest that photo-oxygenation may represent a novel anti-amyloid-beta strategy in Alzheimer's disease, which is compatible with immunotherapy.

Automated summary

The study demonstrated that photo-oxygenation facilitates the clearance of aggregated amyloid-beta from the brains of living Alzheimer's disease model mice, and enhances the microglial degradation of amyloid-beta peptide, suggesting a novel strategy for Alzheimer's disease treatment that may be compatible with immunotherapy.