Orally Administered Benzofuran Derivative Disaggregated Aβ Plaques and Oligomers in the Brain of 5XFAD Alzheimer Transgenic Mouse

Amyloid-beta (A beta) aggregated forms are highly associated with the onset of Alzheimer's disease (AD). A beta abnormally accumulates in the brain and induces neuronal damages and symptoms of AD such as cognitive impairment and memory loss. Since an antibody drug, aducanumab, reduces A beta aggregates and delays clinical decline, clearance of accumulated A beta in the brain is accounted as a therapeutic approach to treat AD. In this study, we synthesized 17 benzofuran derivatives that may disaggregate A beta oligomers and plaques into inert monomers. By a series of A beta aggregation inhibition and aggregates' disaggregation assays utilizing thioflavin T assays and gel electrophoresis, YB-9, 2-((5-methoxy-3-(4-methoxyphenyl)benzofuran-6-yl)oxy)acetic acid, was selected as the final A beta-disaggregator candidate. When it was orally administered to the 8-month-old male transgenic mouse model with five familial AD mutations (5XFAD) via drinking water daily for two months, A beta oligomers and plaques in hippocampus were reduced. Consequently, decreased astrogliosis and rescued synaptic dysfunction were observed in the hippocampus of YB-9-treated 5XFAD mice compared with the untreated transgenic control group.

Automated summary

The study showed that YB-9 administration in a mouse model reduced Aβ oligomers and plaques in the hippocampus, leading to decreased astrogliosis and improved synaptic dysfunction.