Promotion in the Clearance of Aggregated Aβ In Vivo Using Amyloid Selective Photo-Oxygenation Technology

Abstract

Alzheimer’s disease (AD) is characterized by the aggregation and deposition of 2 amyloid proteins: amyloid β peptide (Aβ) and tau protein. Immunotherapies using anti-Aβ antibodies to promote the clearance of aggregated Aβ have recently been highlighted as a promising disease-modifying approach against AD. However, immunotherapy has still some problems, such as low efficiency of delivery into the brain and high costs. We have developed the “amyloid selective photo-oxygenation technology” as a comparable to immunotherapy for amyloids. The photo-oxygenation can artificially attach the oxygen atoms to specific amino acids in amyloid proteins using photocatalyst and light irradiation. We revealed that in vivo photo-oxygenation for living AD model mice reduced the aggregated Aβ in the brain. Moreover, we also showed that microglia were responsible for this promoted clearance of photo-oxygenated Aβ from the brain. These results indicated that our photo-oxygenation technology has the potential as a disease-modifying therapy against AD to promote the degradation of amyloids, resulting in being comparable to immunotherapy. Here, we introduce our technology and its effects in vivo that we showed previously in Ozawa et al., Brain , 2021, as well as a further improvement towards non-invasive in vivo photo-oxygenation described in another publication Nagashima et al., Sci. Adv. , 2021, as expanded discussion.